Tricyclic and heterocyclic derivative compounds and drugs containing these compounds as the active ingredient

ABSTRACT

Tri-heterocyclic compound of formula (I)                  
 
wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1  is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6  etc.; R 3  is carbocyclic ring, heterocyclic ring;
 
and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient.
 
     A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer&#39;s disease, drug addiction or alcohol dependence syndrome etc.

TECHNICAL FIELD

The present invention relates to tri-heterocyclic compounds of formula(I)

wherein all symbols are as hereinafter defined; which is useful as apharmaceutical, and a pharmaceutical comprising them as an activeingredient.

BACKGROUND

Corticotropin Releasing Factor (CRF) was a peptide comprising 41 aminoacid residues and isolated from ovine hypothalamic in 1981. It wassuggested that CRF was released from hypothalamic and controlled asecretion of adrenocorticotropic hormone (ACTH) from hypophysis[Science, 218, 377–379(1982)].

A biological effect is begun from CRF binds to CRF receptor, whichexists on membranous surface of ACTH producing cell in anteriorpituitary. Two subtypes of CRF receptors have been identified, and eachone of these is distributed in a different area of brain. For example, alot of receptor 1 is distributed in hypophysis, hypothalamic, cerebralcortex and a lot of receptor 2 is distributed in septal of brain,hypothalamus nucleus paraventricularis. Besides, receptors are alsodistributed in peripheral organ, for example, heart, gastrointestinal,lung, adrenal medulla, spleen, liver, renal, glandula prostatica.Concretely, receptor 1 is existed in bowel or spleen, receptor 2 isexisted in stomach and especially receptor 2β is existed in heart andskeletal muscle.

ACTH, which is released by a stimulation of CRF, stimulates a secretionof cortisol from adrenal cortex, and relates to a systemic action forreproduction, growth, gastrointestinal function, inflammation, immunesystem, nervous system etc. Consequently, CRF is believed to plays arole as a regulator of these functions.

It was reported that excess CRF was secreted in brain of patient withdepression and anxiety disorders [Science, 226, 1342–1343 (1984);Neuroscience and Behavioral Reviews, 22, 635–651 (1998); J. Endocrinol,160, 1–12 (1999)].

Besides, a relation of CRF and various disorders was reported, forexample, eating disorder [Science, 273, 1561–1564 (1996)], inflammation[Endocrinology, 137, 5747–5750 (1996)], irritable bowel syndrome [Am. J.Physiol, 253, G582–G586 (1987)], drug dependence [Psychopharmacology137, 184–190 (1998)] and ischemia [Soc Neurosci Abstr (November 4–9, NewOrleans), 807.5 (2000)].

On the other hand, CRF has an intimate involvement in stress. Forexample, administration of CRF to the brain elicited same behavior andendocrine response as an animal under stressful conditions [Nature, 297,331 (1982)].

As above, a relationship of CRF and a disorder of central nerve system,neuropsychiatric disorder or a disorder of peripheral organ has beenattracted attention.

Accordingly, an antagonism of CRF receptor is considered to be usefulfor a disease by abnormal secretion of CRF, for example, variousdiseases comprising stress-related disorders. For examples, it isbelieved to be useful for a prevention and/or treatment of depression,single episode depression, recurrent depression, postpartum depression,child abuse induced depression, anxiety, anxiety related disorders (e.g.panic disorder, particular phobia, fear of falling, social phobia,obsessive compulsive disorder), emotional disorder, bipolar disorder,posttraumatic stress disorder, peptic ulcer, diarrhea, constipation,irritable bowl syndrome, inflammatory bowel disease (ulcerative colitis,Crohn's disease), stress-induced gastrointestinal disturbance, nervousemesis, eating disorder (e.g. anorexia nervosa, bulimia nervosa),obesity, stress-induced sleep disorder, pain of muscular fiber inducedsleep disorder, stress-induced immune suppression, stress-inducedheadache, stress-induced fever, stress-induced pain, post operativestress, rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis,thyroid dysfunction, uveitis, asthma, inappropriate anti-diarrheahormone induced disorder, pain, inflammation, allergic disease, headinjury, spinal cord injury, ischemic neuron injury, toxicity neuroninjury, Cushing's disease, seizure, spasm, muscular spasm, epilepsy,ischemic disease, Parkinson's disease, Huntington disease, urinaryincontinence, Alzheimer's disease, senile dementia of Alzheimer type,multi-infarct dementia, amyotrophic lateral sclerosis, hypoglycemia,cardiovascular or heart-related disease (hypertension, tachycardia,congestive heart failure), drug addiction or alcohol dependencesyndrome.

On the other hand, following compounds having an antagonism activity ofCRF were known.

-   (1) In a specification of WO 97/29109, a compound of formula (A)

-   wherein R^(1A) is NR^(4A)R^(5A) or OR^(5A);-   R^(2A) is alkyl, alkyloxy, alkylthio:-   R^(3A) is H, alkyl, alkylsulfonyl, alkylsufoxy or alkylthio;-   R^(4A) is H, alkyl, mono- or di(cycloalkyl)methyl, cycloalkyl,    alkenyl, hydroxyalkyl, alkylcarbonyloxyalkyl or alkyloxyalkyl;-   R^(5A) is alkyl, mono- or di(cycloalkyl)methyl, Ar^(1A)—CH₂,    alkenyl, alkyloxyalkyl, hydroxyalkyl, thienylmethyl, furanylmethyl,    alkylthioalkyl, morpholinyl etc.;-   or R^(4A) and R^(5A) taken together with the nitrogen atom to which    they are attached may form a pyrrolidinyl, piperidinyl,    homopiperidinyl or morpholinyl, optionally substituted with alkyl,    alkyloxyalkyl;-   Ar^(A) is phenyl, phenyl substituted with 1, 2 or 3 substitutes    independently selected from halo, alkyl, trifluoromethyl, hydroxy,    etc.; pyridinyl, pyridinyl substituted with 1, 2 or 3 substitutes    independently selected from halo, alkyl, trifluoromethyl, hydroxy;-   was described as CRF receptor antagonist.-   (2) In a specification of WO 98/03510, a compound of formula (B)

-   wherein A^(B) is N or CR^(B);-   Z^(B) is N or CR^(2B);-   Ar^(B) is selected from phenyl, naphthyl, pyridyl, pyrimidinyl,    triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, etc., each    Ar^(B) optionally substituted with 1 to 5 R^(4B);-   R^(B) is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,    halo, cyano or haloalkyl;-   R^(1B) is H, alkyl, alkenyl, alkynyl, halo, cyano or haloalkyl,    hydroxyalkyl, etc.;-   R^(2B) is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,    hydroxyalkyl, etc.;-   R^(3B) is H, OR^(7B), SH, S(O)_(n)R^(13B), COR^(7B), CO₂R^(7B),    OC(O)R^(13B), NR^(8B)COR^(7B), N(COR^(7B))₂, NR^(8B)CONR^(6B)R^(7B),    NR^(8B)BCO₂R^(13B), NR^(6B)R^(7B), alkyl, alkenyl, alkynyl,    cycloalkyl, cycloalkylalkyl, etc.;-   R^(4B) is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, NO₂,    halo, cyano, haloalkyl, NR^(6B)R^(7B), NR^(8B)COR^(7B), etc.;-   was described as CRF receptor antagonist.-   (3) In a specification of WO 98/08847, a compound of formula (C)

-   wherein the dashed lines is optional double bonds;-   A^(C) is nitrogen or CR^(7C);-   B^(C) is NR^(1C)R^(2C), CR^(1C)R^(2C)R^(10C),    C(═CR^(2C)R^(11C))R^(1C), NHCR^(1C)R^(2C)R^(10C),    OCR^(1C)R^(2C)R^(10C), SCR^(1C)R^(2C)R^(10C),    CR^(2C)R^(10C)NHR^(1C), CR^(2C)R^(10C)OR^(1C), CR^(2C)R^(10C)SR^(1C)    or COR^(2C);-   J^(C) and K^(C) are each independently nitrogen or carbon and both    are not nitrogens;-   D^(C) and E^(C) are each selected, independently, from nitrogen,    CR^(4C), C═O, C═S, sulfur, oxygen, CR^(4C)R^(6C) and NR^(8C);-   G^(C) is nitrogen or carbon;-   The ring containing D^(C), E^(C), G^(C), K^(C) and J^(C) may be a    saturated or unsaturated 5-membered ring and optionally substituted    with one or two double bonds and may optionally contain from one to    three heteroatoms in the ring and may optionally have one or two C═O    or C═S; R^(1C) is alkyl optionally substituted with one or two    substitutes independently selected from hydroxy, fluoro, chloro,    bromo, iodo, O-alkyl, CF₃, C(═O)O-alkyl, OC(═O)alkyl, etc.;-   R^(2C) is alkyl, which may optionally contain from one to three    double or triple bonds, aryl or arylalkyl, cycloalkyl,    cycloalkylalkyl, etc.;-   R^(3C) is H, alkyl, O-alkyl, chloro, fluoro, bromo, iodo,    alkylene-O-alkyl, alkylene-OH or S-alkyl;-   R^(4C) is H, alkyl, fluoro, chloro, bromo, iodo, hydroxy, cyano,    amino, alkylene-OH, CF₃, etc;-   R_(5C) is phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl and    each group is substituted with from one to four substitutes R^(13C),    wherein one to three of said substitutes may be selected,    independently, from fluoro, chloro, alkyl and O-alkyl, and one of    said substitutes may be selected from bromo, iodo, formyl, OH,    alkylene-OH, alkylene-O-alkyl, cyano, CF₃, nitro, amino, alkylamino,    dialkylamino, etc.;-   was described as CRF receptor antagonist.

DISCLOSURE OF INVENTION

The present invention relates to tri-heterocyclic compounds. Moreparticularly, this invention is related to compounds of formula (I)

-   wherein X and Y each independently, is carbon or nitrogen and both    are not nitrogens at the same time;-   W is carbon or nitrogen;-   U and Z each independently, is CR², NR¹³, nitrogen, oxygen, sulfur,    C═O or C═S;-   R² is-   (i) hydrogen,-   (ii) C1–8 alkyl,-   (iii) C2–8 alkenyl,-   (iv) C2–8 alkynyl,-   (v) halogen atom,-   (vi) CF₃,-   (vii) cyano,-   (viii) nitro,-   (ix) NR⁹R¹⁰ in which R⁹ and R¹⁰ each independently,    -   (i) hydrogen,    -   (ii) C1–4 alkyl,    -   (iii) C3–10 mono- or bi-carbocyclic ring,    -   (iv) 3–10 membered mono- or bi-heterocyclic ring containing 1–4        of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or    -   (v) C1–4 alkyl substituted by C3–10 mono- or bi-carbocyclic ring        or 3–10 membered mono- or bi-heterocyclic ring containing 1–4 of        nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s),-   (x) OR¹¹ in which R¹¹ is    -   (i) hydrogen,    -   (ii) C1–4 alkyl,    -   (iii) C5–6 carbocyclic ring,    -   (iv) 5 or 6 membered heterocyclic ring containing 1–2 of        nitrogen(s), 1 of oxygen and/or 1 of sulfur or    -   (v) C1–4 alkyl substituted by C5–6 carbocyclic ring or 5 or 6        membered heterocyclic ring containing 1–2 of nitrogen(s), 1 of        oxygen and/or 1 of sulfur,-   (xi) SH,-   (xii) S(O)_(n)R¹² in which n is 0, 1 or 2, R¹² is    -   (i) C1–4 alkyl,    -   (ii) C5–6 carbocyclic ring,    -   (iii) 5 or 6 membered heterocyclic ring containing 1–2 of        nitrogen(s), 1 of oxygen and/or 1 of sulfur or    -   (iv) C1–4 alkyl substituted by C5–6 carbocyclic ring or 5 or 6        membered heterocyclic ring containing 1–2 of nitrogen(s), 1 of        oxygen and/or 1 of sulfur,-   (xiii) COR¹¹,-   (xiv) COOR¹¹,-   (xv) CONR⁹R¹⁰,-   (xvi) C3–10 mono-or bi-carbocyclic ring,-   (xvii) 3–10 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or-   (xviii) C1–4 alkyl substituted by 1–2 of substitutes selected from    halogen atom, CF₃, OCF₃, cyano, nitro, NR⁹R¹⁰, OR¹¹, ═N—OR¹¹, SH,    S(O)_(n)R², COR¹¹, COOR¹¹, CONR⁹R¹⁰, C3–10 mono- or bi-carbocyclic    ring and 3–10 membered mono- or bi-heterocyclic ring containing 1–4    of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s),-   R¹³ is-   (i) hydrogen,-   (ii) C1–4 alkyl,-   (iii) C2–4 alkenyl,-   (iv) C2–4 alkynyl,-   (v) C3–10 mono- or bi-carbocyclic ring,-   (vi) 3–10 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or-   (vii) C1–4 alkyl substituted by C3–10 mono- or bi-carbocyclic ring    or 3–10 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s),-   is a single bond or a double bond,

is C4–6 carbocyclic ring or 4–6 membered heterocyclic ring containing atleast one of nitrogen, oxygen and sulfur and these rings areunsubstituted or substituted by 1–3 of substitutes selected from C1–4alkyl, C1–4 alkoxy, halogen atom and CF₃,

-   R¹ is-   (i) C1–8 alkyl which is unsubstituted or substituted by 1–5 of R¹⁴,-   (ii) C2–8 alkenyl which is unsubstituted or substituted by 1–5 of    R¹⁴,-   (iii) C2–8 alkynyl which is unsubstituted or substituted by 1–5 of    R¹⁴,-   (iv) NR⁴R⁵ in which R⁴ and R⁵ each independently,    -   (i) hydrogen,    -   (ii) C1–15 alkyl which is unsubstituted or substituted by 1–5 of        R¹⁷,    -   (iii) C2–15 alkenyl which is unsubstituted or substituted by 1–5        of R¹⁷,    -   (iv) C2–15 alkynyl which is unsubstituted or substituted by 1–5        of R¹⁷,    -   (v) C3–15 mono- or bi-carbocyclic ring which is unsubstituted or        substituted by 1–5 of R¹⁸,    -   (vi) 3–15 membered mono- or bi-heterocyclic ring containing 1–4        of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which        is unsubstituted or substituted by 1–5 of R¹⁸,-   (v) OR⁶ in which R⁶ is    -   (i) hydrogen,    -   (ii) C1–10 alkyl,    -   (iii) C2–10 alkenyl,    -   (iv) C2–10 alkynyl,    -   (v) C3–15 mono- or bi-carbocyclic ring which is unsubstituted or        substituted by 1–5 of R¹⁸,    -   (vi) 3–15 membered mono- or bi-heterocyclic ring containing 1–4        of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which        is unsubstituted or substituted by 1–5 of R¹⁸,    -   (vii) C1–4 alkyl substituted by 1–2 of substitutes selected from        halogen atom, CF₃, OCF₃, cyano, nitro, NR⁹R¹⁰, OR¹¹, ═N—OR¹¹,        SH, S(O)_(n)R¹², COR¹¹, COOR¹¹, CONR⁹R¹⁰, C3–10 mono- or        bi-carbocyclic ring which is unsubstituted or substituted by 1–5        of R¹⁸, and 3–10 membered mono- or bi-heterocyclic ring        containing 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of        sulfur(s) which is unsubstituted or substituted by 1–5 of R¹⁸,-   (vi) SH,-   (vii) S(O)_(n)R⁷ in which n is as hereinbefore defined, R⁷ is    -   (i) C1–8 alkyl,    -   (ii) C3–10 mono- or bi-carbocyclic ring which is unsubstituted        or substituted by 1–5 of R¹⁸,    -   (iii) 3–10 membered mono- or bi-heterocyclic ring containing 1–4        of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which        is unsubstituted or substituted by 1–5 of R¹⁸,    -   (iv) C1–4 alkyl substituted by C3–10 mono- or bi-carbocyclic        ring, which is is unsubstituted or substituted by 1–5 of R¹⁸ or        3–10 membered mono- or bi-heterocyclic ring containing 1–4 of        nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which is        unsubstituted or substituted by 1–5 of R¹⁸,-   (viii) COR⁶,-   (ix) COOR⁶,-   (x) CONR⁴R⁵,-   (xi) NR⁸COR^(6a) in which R^(6a) is    -   (i) hydrogen,    -   (ii) C1–10 alkyl,    -   (iii) C2–10 alkenyl,    -   (iv) C2–10 alkynyl or    -   (v) C1–4 alkyl substituted by 1–2 of substitutes selected from        halogen atom, CF₃, OCF₃, cyano, nitro, NR⁹R¹⁰, OR^(11a),        ═N—OR¹¹, SH, S(O)_(n)R², COR¹¹, COOR¹¹ and CONR⁹R¹⁰,-   (xii) NR⁸COOR⁶ in which R⁶ is as hereinbefore defined, R⁸ is    -   (i) hydrogen,    -   (ii) C1–8 alkyl,    -   (iii) C2–8 alkenyl,    -   (iv) C2–8 alkynyl,    -   (v) C3–10 mono- or bi-carbocyclic ring which is unsubstituted or        substituted by 1–5 of R⁸,    -   (vi) 3–10 membered mono- or bi-heterocyclic ring containing 1–4        of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which        is unsubstituted or substituted by 1–5 of R¹⁸ or    -   (vii) C1–4 alkyl substituted by 1–2 of substitutes selected from        halogen atom, CF₃, OCF₃, cyano, nitro, NR⁹R¹⁰, OR¹¹, ═N—OR¹¹,        SH, S(O)_(n)R¹², COR¹¹, COOR¹¹, CONR⁹R¹⁰, C3–10 mono- or        bi-carbocyclic ring which is unsubstituted or substituted by 1–5        of R¹⁸, and 3–10 membered mono- or bi-heterocyclic ring        containing 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of        sulfur(s) which is unsubstituted or substituted by 1–5 of R¹⁸,-   (xiii) NR⁸CONR⁴R⁵,-   (xiv) C3–15 mono- or bi-carbocyclic ring which is unsubstituted or    substituted by 1–5 of R¹⁵ or-   (xv) 3–15 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which is    unsubstituted or substituted by 1–5 of R¹⁵,-   R^(11a) is (i) hydrogen, (ii) C1–4 alkyl or (iii) C1–4 alkyl    substituted by C5–6 carbocyclic ring o 5 or 6 membered heterocyclic    ring containing 1–2 of nitrogen(s), 1 of oxygen and/or 1 of sulfur,-   R¹⁴ is (a) halogen atom, (b) CF₃, (c) OCF₃, (d) cyano, (e)    nitro, (f) NR⁴R⁵, (g) OR⁶, (h) ═N—OR⁶, (j) SH, (k) S(O)_(n)R⁷, (l)    COR⁶, (m) COOR⁶, (n) CONR⁴R⁵, (O)NR⁸COR⁶, (p) ONR⁸COOR⁶, (q)    NR⁸CONR⁴R⁵, (r) C3–15 mono- or bi-carbocyclic ring which is    unsubstituted or substituted by 1–5 of R¹⁵ or (s) 3–15 membered    mono- or bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of    oxygen(s) and/or 1–2 of sulfur(s) which is unsubstituted or    substituted by 1–5 of R¹⁵,-   R¹⁵ is (a) C1–8 alkyl, (b) C2–8 alkenyl, (c) C2–8 alkynyl, (d) C1–4    alkoxy(C1–4)alkyl, (e) halogen atom, (f) CF₃, (g) OCF₃, (h)    cyano, (j) nitro, (k) NR⁴R⁵, (l) OR⁶, (m) SH, (n) S(O)_(n)R⁷, (o)    COR⁶, (p) COOR⁶, (q) CONR⁴R⁵, (r) NR⁸COR⁶, (s) NR⁸COOR⁶, (t)    NR⁸CONR⁴R⁵, (u) C3–10 mono- or bi-carbocyclic ring which is    unsubstituted or substituted by 1–5 of R²⁰, (v) 3–10 membered mono-    or bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of    oxygen(s) and/or 1–2 of sulfur(s) which is unsubstituted or    substituted by 1–5 of R²⁰ or (w) C1–4 alkyl substituted by 1–2 of    substitutes selected from halogen atom, CF₃, OCF₃, cyano, nitro,    NR⁴R⁵, OR⁶, ═N—OR⁶, SH, S(O)_(n)R⁷, COR⁶, COOR⁶, CONR⁴R⁵, NR⁸COR⁶,    NR⁸COOR⁶, NR⁸CONR⁴R⁵, C3–10 mono- or bi-carbocyclic ring which is    unsubstituted or substituted by 1–5 of R²⁰, and 3–10 membered mono-    or bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of    oxygen(s) and/or 1–2 of sulfur(s) which is unsubstituted or    substituted by 1–5 of R²⁰, R¹⁷ is (a) halogen atom, (b) CF₃, (c)    OCF₃, (d) cyano, (e) nitro, (f) NR⁹R¹⁰, (g) OR^(11a), (h)    ═N—OR¹¹, (j) SH, (k) S(O)_(n)R¹², (l) COR¹¹, (m) COOR¹¹, (n)    CONR⁹R¹⁰, (O)NR⁸COR¹¹, (p) NR⁸COOR¹¹, (q) NR⁸CONR⁹R¹⁰, (r) C3–15    mono- or bi-carbocyclic ring which is unsubstituted or substituted    by 1–5 of R^(18a) or (s) 3–15 membered mono- or bi-heterocyclic ring    containing 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of    sulfur(s) which is unsubstituted or substituted by 1–5 of R^(18a),-   R¹⁸ is (a) C1–4 alkyl, (b) C2–4 alkenyl, (c) C2–4 alkynyl, (d)    halogen atom, (e) CF₃, (f) OCF₃, (g) cyano, (h) nitro, (j) SH, (k)    S(O)_(n)R¹², (l) NR⁹R¹⁰, (m) OR¹¹, (n) COR¹¹, (O)COOR¹¹, (p)    CONR⁹R¹⁰, (q) C5–6 carbocyclic ring, (r) 5 or 6 membered    heterocyclic ring containing 1–2 of nitrogen(s), 1 of oxygen and/or    1 of sulfur or (s) C1–4 alkyl substituted by C5–6 carbocyclic ring    or 5 or 6 membered heterocyclic ring containing 1–2 of nitrogen(s),    1 of oxygen and/or 1 of sulfur,-   R^(18a) is (a) C1–4 alkyl, (b) C2–4 alkenyl, (c) C2–4 alkynyl, (d)    halogen atom, (e) CF₃, (f) OCF₃, (g) cyano, (h) nitro, (j) SH, (k)    S(O)_(n)R¹², (l) NR⁹R¹⁰, (m) OR^(11a), (n) COR¹¹, (O)COOR¹¹ or (p)    CONR⁹R¹⁰,-   R¹⁹ is C1–4 alkyl, C1–4 alkoxy, halogen atom, CF₃, OCF₃, cyano,    nitro, amino, NH(C1–4alkyl) or N(C1–4 alkyl)₂,-   R³ is (i) C5–10 mono- or bi-carbocyclic ring substituted by 1–5 of    R¹⁶ or (ii) 5–10 membered mono- or bi-heterocyclic ring containing    1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)    substituted by 1–5 of R¹⁶,-   R¹⁶ is (a) C1–8 alkyl,-   (b) C2–8 alkenyl,-   (c) C2–8 alkynyl,-   (d) halogen atom,-   (e) CF₃,-   (f) OCF₃,-   (g) cyano,-   (h) nitro,-   (j) NR⁹R¹⁰,-   (k) OR¹¹,-   (l) SH,-   (m) S(O)_(n)R¹², which is excepted phenylthio,-   (n) COR¹¹,-   (o) COOR¹¹,-   (p) CONR⁹R¹⁰,-   (q) NR⁸COR¹¹,-   (r) NR⁸COOR¹¹,-   (s) NR⁸CONR⁹R¹⁰,-   (t) C3–10 mono- or bi-carbocyclic ring,-   (u) 3–10 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)-   (v) C1–4 alkyl substituted by 1–2 of substitutes selected from    halogen atom, CF₃, OCF₃, cyano, nitro, NR⁹R¹⁰, OR¹¹, ═N—OR¹¹, SH,    S(O)_(n)R¹², COR¹¹, COOR¹¹, CONR⁹R¹⁰, NR⁸COR¹¹, NR⁸COOR¹¹,    NR⁸CONR⁹R¹⁰, C3–10 mono- or bi-carbocyclic ring, and 3–10 membered    mono- or bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of    oxygen(s) and/or 1–2 of sulfur(s),-   with the proviso that (1) when X and W are carbons, Y and Z are    nitrogens, U is CR⁴ and R¹ is OR⁶, then R³ is not phenyl substituted    by 1 of halogen atom, phenyl substituted by 1 of trifluoromethyl and    phenyl substituted by trifluoromethyl and nitro, (2) when X, Y and Z    are carbons and U and W are nitrogens, then R³ is C5–10 mono- or    bi-carbocyclic ring substituted by 1–5 of R¹⁶;-   a pharmaceutically acceptable salt thereof or a hydrate thereof,-   (2) a process for the preparation thereof and-   (3) a pharmaceutical composition comprising them as CRF receptor    antagonist.

In the specification, C1–4 alkyl means methyl, ethyl, propyl, butyl andisomeric groups thereof.

In the specification, C1–8 alkyl means methyl, ethyl, propyl, butyl,pentyl, hexyl, heptyl, octyl and isomeric groups thereof.

In the specification, C1–15 alkyl means methyl, ethyl, propyl, butyl,pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,tetradecyl, pentadecyl and isomeric groups thereof.

In the specification, C1–4 alkoxy means methoxy, ethoxy, propoxy, butoxyand isomeric groups thereof.

In the specification, C2–4 alkenyl means vinyl, propenyl, butenyl andisomeric groups thereof.

In the specification, C2–8 alkenyl means ethyl, propyl, butyl, pentyl,hexyl, heptyl, octyl having 1–3 of double bond(s) and isomeric groupsthereof. For example, vinyl, propenyl, butenyl, pentenyl, hexenyl,hexadienyl, heptenyl, heptadienyl, octenyl, octadienyl.

In the specification, C2–15 alkenyl means ethyl, propyl, butyl, pentyl,hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,tetradecyl, pentadecyl having 1–3 of double bond(s) and isomeric groupsthereof. For example, vinyl, propenyl, butenyl, pentenyl, hexenyl,hexadienyl, heptenyl, heptadienyl, octenyl, octadienyl, nonenyl,nonadienyl, decenyl, decadienyl, undecenyl, dodecenyl, tridecenyl,tetradecenyl, pentadecenyl.

In the specification, C2–4 alkynyl means ethynyl, propynyl, butynyl andisomeric groups thereof.

In the specification, C2–8 alkynyl means ethyl, propyl, butyl, pentyl,hexyl, heptyl, octyl having 1–3 of triple bond(s) and isomeric groupsthereof. For example, ethynyl, propynyl, butynyl, pentynyl, hexynyl,hexadiynyl, heptynyl, heptadiynyl, octynyl, octadiynyl.

In the specification, C2–15 alkynyl means ethyl, propyl, butyl, pentyl,hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl,tetradecyl, pentadecyl having 1–3 of triple bond(s) and isomeric groupsthereof. For example, ethynyl, propynyl, butynyl, pentynyl, hexynyl,hexadiynyl, heptynyl, heptadiynyl, octynyl, octadiynyl, nonynyl,decynyl, undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl.

In the specification, halogen atom is fluorine, chlorine, bromine andiodine.

In the specification, C1–4 alkoxy(C1–4)alkyl means methyl, ethyl,propyl, butyl, and isomeric groups thereof substituted by one ofmethoxy, ethoxy, propoxy, butoxy and isomeric groups thereof.

In the specification, C4–6 carbocyclic ring is C4–6 carbocyclic aryl orpartially or fully saturated thereof. For example, cyclobutane,cyclopentane, cyclohexane, cyclopentene, cyclohexene, cyclopentadiene,cyclohexadiene, benzene.

In the specification, C5–6 carbocyclic ring is C5–6 carbocyclic aryl orpartially or fully saturated thereof. For example, cyclopentane,cyclohexane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene,benzene.

In the specification, C3–10 mono- or bi-carbocyclic ring is C3–10 cmono- or bi-carbocyclic aryl or partially or fully saturated thereof.For example, cyclopropane, cyclobutane, cyclopentane, cyclohexane,cycloheptane, cyclopentene, cyclohexene, cyclopentadiene,cyclohexadiene, benzene, pentalene, indene, naphthalene, azulene,perhydropentalene, indan, perhydroindene, teterahydronaphthalene,perhydronaphthalene, perhydroazulene.

In the specification, C3–15 mono- or bi-carbocyclic ring is C3–15 mono-or bi-carbocyclic aryl or partially or fully saturated thereof orbridged bi-carbocyclic ring. For example, cyclopropane, cyclobutane,cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene,cyclopentadiene, cyclohexadiene, benzene, pentalene, indene,naphthalene, azulene, heptalene, perhydropentalene, indan,perhydroindene, teterahydronaphthalene, perhydronaphthalene,perhydroazulene, perhydroheptalene, bicyclo[3.1.1]heptane.

In the specification, C5–10 mono- or bi-carbocyclic ring is C5–10 mono-or bi-carbocyclic aryl or partially or fully saturated thereof. Forexample, cyclopentane, cyclohexane, cycloheptane, cyclopentene,cyclohexene, cycloheptene, cyclopentadiene, cyclohexadiene,cycloheptadiene, benzene, pentalene, indene, naphthalene, azulene,perhydropentalene, indan, perhydroindene, teterahydronaphthalene,perhydronaphthalene, perhydroazulene.

In the specification, 4–6 membered heterocyclic ring containing at leastone of nitrogen, oxygen and sulfur is 4–6 membered heterocyclic arylcontaining at least one of nitrogen, oxygen and sulfur or partially orfully saturated thereof. For example, azetidine, pyrrolidine, pyrroline,pyrrole, tetrahydrofuran, dihydrofuran, furan, tetrahydrothiophene,dihydrothiophene, thiophene, piperidine, dihydropyridine, pyridine,tetrahydropyran, dihydropyran, pyran, tetrahydrothiopyran,dihydrothiopyran, thiopyran.

In the specification, 5 or 6 membered heterocyclic ring containing 1–2of nitrogen(s), 1 of oxygen and/or 1 of sulfur is 5 or 6 memberedheterocyclic aryl containing 1–2 of nitrogen(s), 1 of oxygen and/or 1 ofsulfur or partially or fully saturated thereof. For example, pyrrole,imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, furan,pyran, thiophene, thiain (thiopyran), oxazole, isoxazole, thiazole,isothiazole, pyrroline, pyrrolidine, piperidine, imidazoline,imidazolidine, pyrazoline, pyrazolidine, piperazine, perhydropyrimidine,perhydropyridazine, dihydrofuran, tetrahydrofuran, tetrahydropyran,dihydrothiophene, tetrahydrothiophene, tetrahydrothiain, morpholine,thiomorpholine.

In the specification, 3–10 membered mono- or bi-heterocyclic ringcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is 3–10 membered mono- or bi-heterocyclic aryl containing 1–4 ofnitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or partially orfully saturated thereof. 3–10 membered mono- or bi-heterocyclic arylcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is, for example, pyrrole, imidazole, pyrazole, triazole, tetrazole,pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan,pyran, oxepine, thiophene, thiain (thiopyran), thiepine, oxazole,isoxazole, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine,thiazole, isothiazole, thiadiazole, thiazine, thiadiazine, thiazepine,thiadiazepine, indole, isoindole, indolizine, benzofuran, isobenzofuran,benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline,quinolizine, phthalazine, naphthyridine, quinoxaline, quinazoline,cinnoline, benzoxazole, benzoxadiazole, benzothiazole, benzimidazole,benzofurazan, benzothiadiazole, benzotriazole.

The above partially or fully saturated 3–10 membered mono- orbi-heterocyclic aryl containing 1–4 of nitrogen(s), 1–2 of oxygen(s)and/or 1–2 of sulfur(s) is, for example, aziridine, azetine, azetidine,pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline,pyrazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine,piperidine, piperazine, dihydropyridine, tetrahydropyridine,dihydropyrazine, tetrahydropyrazine, dihydropyrimidine,tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine,tetrahydropyridazine, perhydropyridazine, dihydroazepine,tetrahydroazepine, perhydroazepine, dihydrodiazepine,tetrahydrodiazepine, perhydrodiazepine, oxirane, oxetane, dihydrofuran,tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooxepine,tetrahydrooxepine, perhydrooxepine, thiirane, thietane,dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihyrdothiopyran),tetrahydrothiain (tetrahydrothiopyran), dihydrothiepine,tetrahydrothiepine, perhydrothiepine, oxazoline (dihydrooxazole),oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole,oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole),thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole),dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole,dioxolane, dioxane, dioxazine, dioxaindan, chroman, isochroman.

In the specification, 3–15 membered mono- or bi-heterocyclic ringcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is 3–15 membered mono- or bi-heterocyclic aryl containing 1–4 ofnitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or partially orfully saturated thereof. 3–15 membered mono- or bi-heterocyclic arylcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is, for example, pyrrole, imidazole, pyrazole, triazole, tetrazole,pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan,pyran, oxepine, thiophene, thiain (thiopyran), thiepine, oxazole,isoxazole, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine,thiazole, isothiazole, thiadiazole, thiazine, thiadiazine, thiazepine,thiadiazepine, indole, isoindole, indolizine, benzofuran, isobenzofuran,benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline,quinolizine, phthalazine, naphthyridine, quinoxaline, quinazoline,cinnoline, benzoxazole, benzoxadiazole, benzothiazole, benzimidazole,benzazepine, benzodiazepine, benzotriazole, benzoxazepine,benzoxadiazepine, benzothiazepine, benzothiadiazole, benzothiadiazepine,benzofurazan.

The above partially or fully saturated 3–15 membered mono- orbi-heterocyclic aryl containing 1–4 of nitrogen(s), 1–2 of oxygen(s)and/or 1–2 of sulfur(s) is, for example, aziridine, azetine, azetidine,pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline,pyrazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine,piperidine, piperazine, dihydropyridine, tetrahydropyridine,dihydropyrazine, tetrahydropyrazine, dihydropyrimidine,tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine,tetrahydropyridazine, perhydropyridazine, dihydroazepine,tetrahydroazepine, perhydroazepine, dihydrodiazepine,tetrahydrodiazepine, perhydrodiazepine, oxirane, oxetane, dihydrofuran,tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooxepine,tetrahydrooxepine, perhydrooxepine, thiirane, thietane,dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihyrdothiopyran),tetrahydrothiain (tetrahydrothiopyran), dihydrothiepine,tetrahydrothiepine, perhydrothiepine, oxazoline (dihydrooxazole),oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole,oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole),thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole),dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole,dihydrobenzazepine, tetrahydrobenzazepine, dihydrobenzodiazepine,tetrahydrobenzodiazepine, dihydrobenzoxazepine,tetrahyclrobenzoxazepine, dioxolane, dioxane, dioxazine, dioxaindan,chroman, isochroman.

In the specification, 5–10 membered mono- or bi-heterocyclic ringcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is 5–10 membered mono- or bi-heterocyclic aryl containing 1–4 ofnitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) or partially orfully saturated thereof. 5–10 membered mono- or bi-heterocyclic arylcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)is, for example, pyrrole, imidazole, pyrazole, triazole, tetrazole,pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan,pyran, oxepine, thiophene, thiain (thiopyran), thiepine, oxazole,isoxazole, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine,thiazole, isothiazole, thiadiazole, thiazine, thiadiazine, thiazepine,thiadiazepine, indole, isoindole, indolizine, benzofuran, isobenzofuran,benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline,quinolizine, phthalazine, naphthyridine, quinoxaline, quinazoline,cinnoline, benzoxazole, benzoxadiazole, benzothiazole, benzimidazole,benzofurazan, benzothiadiazole, benzotriazole.

The above partially or fully saturated 5–10 membered mono- orbi-heterocyclic aryl containing 1–4 of nitrogen(s), 1–2 of oxygen(s)and/or 1–2 of sulfur(s) is, for example, pyrroline, pyrrolidine,imidazoline, imidazolidine, pyrazoline, pyrazolidine, triazoline,triazolidine, tetrazoline, tetrazolidine, piperidine, piperazine,dihydropyridine, tetrahydropyridine, dihydropyrazine,tetrahydropyrazine, dihydropyrimidine, tetrahydropyrimidine,perhydropyrimidine, dihydropyridazine, tetrahydropyridazine,perhydropyridazine, dihydroazepine, tetrahydroazepine, perhydroazepine,dihydrodiazepine, tetrahydrodiazepine, perhydrodiazepine, oxirane,oxetane, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran,dihydrooxepine, tetrahydrooxepine, perhydrooxepine, thiirane, thietane,dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihyrdothiopyran),tetrahydrothiain (tetrahydrothiopyran), dihydrothiepine,tetrahydrothiepine, perhydrothiepine, oxazoline (dihydrooxazole),oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole,oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole),thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole),dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole,dioxolane, dioxane, dioxazine, dioxaindan, chroman, isochroman.

In the compound of formula (I) of the present invention,

is saturated, partially saturated or unsaturated 5 membered carbocyclicring or heterocyclic ring. X and Y in the ring may be all combinationsthat X is carbon and Y is nitrogen, X is nitrogen and Y is carbon andboth of X and Y are carbons. Concretely, following combinations arepreferable.

-   (i) X is carbon, Y is nitrogen, each of U and Z is carbon or    nitrogen and W is carbon,-   (ii) X is nitrogen, Y is carbon, each of U and Z is carbon or    nitrogen and W is carbon,-   (iii) each of X and Y is carbon, each of U and W is carbon or    nitrogen and Z is carbon,-   (iv) each of X and Y are carbon, U is nitrogen and Z is oxygen or    sulfur, U is oxygen or sulfur, Z is nitrogen and W is carbon, or-   (v) each of X and Y is carbon, each of Z and W is nitrogen and U is    C═O or C═S.

More preferable combination is

-   (i-1) each of X, U and W is carbon, and each of Y and Z is nitrogen,-   (i-2) each of X, Z and W is carbon, and each of Y and U is nitrogen,-   (i-3) each of X, Z, U and W is carbon and Y is nitrogen,-   (ii-1) each of X, Z and U is nitrogen, and each of Y and W is    carbon,-   (ii-2) each of X and Z is nitrogen, and each of Y, U and W is    carbon,-   (ii-3) each of X and U is nitrogen, and each of Y, Z and W is    carbon,-   (ii-4) X is nitrogen, and each of Y, Z, U and W is carbon,-   (iii-1) each of X, Y and Z is carbon, and each of U and W is    nitrogen,-   (iii-2) each of X, Y, Z and U is carbon and W is nitrogen,-   (iv-1) each of X, Y and W is carbon, Z is oxygen and U is nitrogen,-   (iv-2) each of X, Y and W is carbon, Z is sulfur and U is nitrogen,-   (iv-3) each of X, Y and W is carbon, Z is nitrogen and U is oxygen,-   (iv-4) each of X, Y and W is carbon, Z is nitrogen and U is sulfur,-   (v-1) each of X and Y is carbon, each of Z and W is nitrogen and U    is C═O, or-   (v-2) each of X and Y is carbon, each of Z and W is nitrogen and U    is C═S.

In the compound of formula (I) of the present invention, followingcompounds of formula (I-i)–(I-xxvi) are showed as concretely compounds.

In the compound of formula (I-i)–(I-xxvi), following compounds arepreferable.

In the compound of formula (I) of the present invention, C4–6carbocyclic ring or 4–6 membered heterocyclic ring containing at leastone of nitrogen, oxygen and sulfur presented by

is C4–6 carbocyclic aryl or partially or fully saturated thereof, or 4–6membered heterocyclic aryl containing at least one of nitrogen, oxygenand sulfur or partially or fully saturated thereof.

The following are preferable as A ring:

wherein G is O, S or NH; R^(x) is C1–4 alkyl, C1–4 alkoxy, halogen atomor CF₃; m is 0–3.

In the compound of formula (I) of the present invention, preferable R¹is

-   (i) C1–8 alkyl which is unsubstituted or substituted by 1–5 of R¹⁴,-   (ii) C2–8 alkenyl which is unsubstituted or substituted by 1–5 of    R¹⁴,-   (iii) C2–8 alkynyl which is unsubstituted or substituted by 1–5 of    R¹⁴,-   (iv) NR⁴R⁵,-   (v) OR⁶,-   (vi) C3–15 mono- or bi-carbocyclic ring which is unsubstituted or    substituted by 1–5 of R¹⁵ or-   (vii) 3–15 membered mono- or bi-heterocyclic ring containing 1–4 of    nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s) which is    unsubstituted or substituted by 1–5 of R¹⁵.

A preferable combination of R⁴ and R⁵ in NR⁴R⁵ of the above preferableR¹ is

-   (a) R⁴ is (i) hydrogen and R⁵ is (ii) C1–15 alkyl which is    unsubstituted or substituted by 1–5 of R¹⁷, (iii) C2–15 alkenyl    which is unsubstituted or substituted by 1–5 of R⁷, (iv) C2–15    alkynyl which is unsubstituted or substituted by 1–5 of R¹⁷, (v)    C3–15 mono- or bi-carbocyclic ring which is unsubstituted or    substituted by 1–5 of R¹⁸ or (vi) 3–15 membered mono- or    bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of oxygen(s)    and/or 1–2 of sulfur(s) which is unsubstituted or substituted by 1–5    of R¹⁸ or-   (b) R⁴ is (ii) C1–15 alkyl which is unsubstituted or substituted by    1–5 of R¹⁷, (iii) C2–15 alkenyl which is unsubstituted or    substituted by 1–5 of R¹⁷, (iv) C2–15 alkynyl which is unsubstituted    or substituted by 1–5 of R¹⁷ or (v-1) C3–6 mono-carbocyclic ring and    R⁵ is (ii) C1–15 alkyl which is unsubstituted or substituted by 1–5    of R¹⁷, (iii) C2–15 alkenyl which is unsubstituted or substituted by    1–5 of R¹⁷, (iv) C2–15 alkynyl which is unsubstituted or substituted    by 1–5 of R¹⁷, (v) C3–15 mono- or bi-carbocyclic ring which is    unsubstituted or substituted by 1–5 of R¹⁸ or (vi) 3–15 membered    mono- or bi-heterocyclic ring containing 1–4 of nitrogen(s), 1–2 of    oxygen(s) and/or 1–2 of sulfur(s) which is unsubstituted or    substituted by 1–5 of R¹⁸.

It is preferable that 3–15 membered mono- or bi-heterocyclic ringcontaining 1–4 of nitrogen(s), 1–2 of oxygen(s) and/or 1–2 of sulfur(s)which is unsubstituted or substituted by 1–5 of R¹⁵ of the abovepreferable R¹, bonds through nitrogen atom in the ring. That is group:

which is unsubstituted or substituted by 1–5 of R¹⁵, and this group is3–15 membered mono- or bi-heterocyclic ring containing one of nitrogennecessarily, and furthermore optionally containing one of nitrogen,oxygen or sulfur. Concretely, there are following heterocyclic ringswhich is unsubstituted or substituted by 1–5 of R¹⁵.

As specific compounds of the present invention, there are compoundsdescribed in Examples hereinafter and a pharmaceutically acceptable saltthereof.

Unless otherwise specified, all isomers are included in the presentinvention. For example, alkyl, alkoxy, alkylene and alkynyl includestraight and branched isomers. Isomers based on double bond, ring, fusedring (E, Z, cis, trans), isomers resulting from the presence ofasymmetric carbon(s) (R-configuration, S-configuration, α-configuration,β-configuration, enantiomers, diastereoisomers), optically activecompounds having optical rotation (D, L, d, l-configuration), polarcompounds obtained by chromatographic separations (highly polarcompound, less polar compound), equilibrium compounds, the mixtures areexisted by free ratio, racemic mixtures are included in the presentinvention.

[Salt]

The compound of the present invention of formula (I) may be convertedinto a corresponding pharmaceutically acceptable salt by known methods.In the present invention, pharmaceutically acceptable salts are salts ofalkali metals, salts of alkaline-earth metals, ammonium salts, aminesalts, acid addition salts.

Non-toxic and water-soluble salts are preferable. Appropriate salts are,salts of alkali metals, such as potassium, sodium; salts ofalkaline-earth metals, such as calcium, magnesium; ammonium salts,pharmaceutically acceptable organic amines, such as tetramethylammonium,triethylamine, methylamine, dimethylamine, cyclopentylamine,benzylamine, phenethylamine, piperidine, monoethanolamine,diethanolamine, tris(hydroxymethyl)methylaminomethane, lysine, arginine,N-methyl-D-glucamine. A salt of alkali metal is preferable.

Non-toxic and water-soluble acid addition salts are preferable.Appropriate acid addition salts are, salts of inorganic acids, such ashydrochloride, hydrobromide, sulfate, phosphate, nitrate; salts oforganic acid, such as acetate, trifluoroacetate, lactate, tartrate,oxalate, fumarate, maleate, citrate, benzoate, methanesulphonate,ethanesulphonate, benzenesulphonate, toluenesulphonate, isethionate,glucuronate, gluconate.

The compound of formula (I) of the present invention and salts thereofmay be converted into the corresponding hydrates by conventional means.

Preparation of the Compound of the Present Invention

The present compound of formula (I) may be prepared, for example, by thefollowing method.

(A) In the compound of formula (I), the compound in which R¹ is OH, andR² and R³ is not OH, cyano, ═N—OR¹¹ or a group containing OH, cyano or═N—OR¹¹, that is the compound of formula (I-A)

wherein each of Z^(a), U^(a) and R^(3-a) is same meaning as Z, U and R³,with the proviso that they are not OH, cyano, ═N—OR¹¹ or a groupcontaining OH, cyano or ═N—OR¹¹; the other symbols are as hereinbeforedefined;may be prepared by reacting the compound of formula (II-1)

wherein all symbols are as hereinbefore defined;with the compound of formula (III-1)

wherein A^(a) ring is saturated or partially saturated C4–6 carbocyclicring or 4–6 membered heterocyclic ring, Et is ethyl, the other symbolsare as hereinbefore defined;or successively, subjecting to oxidative reaction.

The above reaction of the compound of formula (II) and the compound offormula (III) is known, for example, it is carried out in an organicsolvent (e.g. acetic acid) at from room temperature to refluxtemperature.

Oxidative reaction is known, for example, it is carried out in anorganic solvent (e.g. diphenyl ether), using a metal catalyst (e.g.palladium carbon, palladium, palladium hydroxide, palladium acetate,palladium black), at 0° C.˜250° C.

(B) In the compound of formula (I), the compound in which R¹ is not OH,and cyano, ═N—OR⁶ or a group containing cyano or ═N—OR¹¹, and C3–10mono-, or bi-carbocyclic ring, 3–10 membered mono-, or bi-heterocyclicring containing 1–4 of nitrogen(S), 1–2 of oxygen(s) and/or 1–2 ofsulfur(s), R² and R³ is not OH, cyano, ═N—OR¹¹ or a group containing OH,cyano or ═N—OR¹¹, that is the compound of formula (I-B)

wherein R^(1-a) is same meaning as R¹, with the proviso that it is notOH, and cyano, ═N—OR⁶ or a group containing cyano or ═N—OR¹¹, and C3–10mono-, or bi-carbocyclic ring, 3–10 membered mono-, or bi-heterocyclicring containing 1–4 of nitrogen(S), 1–2 of oxygen(s) and/or 1–2 ofsulfur(s); the other symbols are as hereinbefore defined;may be prepared by reacting the compound of formula (IV)

wherein X is halogen atom, the other symbols are as hereinbeforedefined; with the compound of formula (V-1)H—R^(1-ab)  (V-1)wherein R^(1-ab) is same meaning as R¹, with the proviso that it is notOH, and cyano, ═N—OR⁶ or a group containing cyano or ═N—OR⁶, and C3–10mono-, or bi-carbocyclic ring, 3–10 membered mono-, or bi-heterocyclicring containing 1–4 of nitrogen(S), 1–2 of oxygen(s) and/or 1–2 ofsulfur(s);or successively, subjecting to oxidative reaction, orwith the compound of formula (V-2)R^(1-ac)  (V-2)wherein R^(1-ac) is C3–10 mono-, or bi-carbocyclic ring, 3–10 memberedmono-, or bi-heterocyclic ring containing 1–4 of nitrogen(S), 1–2 ofoxygen(s) and/or 1–2 of sulfur(s);or successively, subjecting to oxidative reaction.

The above reaction of the compound of formula (IV) and the compound offormula (V-1) is known, for example, it is carried out in an organicsolvent (e.g. isopropyl alcohol, toluene, ethanol, tetrahydrofuran) orwithout a solvent, optionally in the presence of a base (e.g. sodiumhydroxide, sodium ethoxide) at 0˜200° C.

The above reaction of the compound of formula (IV) and the compound offormula (V-2) is known, for example, it is carried out in an organicsolvent (e.g. dimethoxyethane, dimethylformaide), in the presence of acatalyst (e.g. palladium acetate) using a phosphine compound (e.g.triphenylphosphine) at 20° C.˜reflux temperature.

Oxidative reaction is carried out by the above method.

On the other hand, in the compound of formula (I-B), the compound inwhich R^(1-a) is C1–4 alkyl substituted by 1–2 of OR⁶ or CONR⁴R⁵, thatis the compound (I-B-1)

wherein R^(1-a-1) is C1–4 alkyl substituted by 1–2 of OR⁶ or CONR⁴R⁵ andthe other symbols are as hereinbefore defined;may be also prepared by subjecting to reductive reaction the compound offormula (I-B-2)

wherein R^(1-a-2) is C1–4 alkyl substituted 1–2 of COOR⁶ and the othersymbols are as hereinbefore defined;or after reductive reaction, by reacting with the compound formula (VI)X—R^(6-a-2)  (VI)wherein R^(6-a-2) is (i) C1–10 alkyl, (ii) C2–10 alkenyl, (iii) C2–10alkynyl, (iv) C3–15 mono-, or bi-carbocyclic ring which is substitutedby 1–5 of R¹⁸ or unsubstituted, (v) 3–15 membered mono-, orbi-heterocyclic ring containing 1–4 of nitrogen(S), 1–2 of oxygen(s)and/or 1–2 of sulfur(s) which is substituted by 1–5 of R¹⁸ orunsubstituted, or (vi) C1–4 alkyl substituted by 1–2 of the group(s)selected from C3–10 mono-, or bi-carbocyclic ring which is substitutedby 1–5 of R¹⁸ or unsubstituted and 3–10 membered mono-, orbi-heterocyclic ring containing 1–4 of nitrogen(S), 1–2 of oxygen(s)and/or 1–2 of sulfur(s) which is substituted by 1–5 of R¹⁸ orunsubstituted;or with the compound formula (VI)HNR⁹R¹⁰  (VII)wherein all symbols are as hereinbefore defined.

Reductive reaction is known, for example, it is carried out in anorganic solvent (e.g. diethyl ether, methylene chloride, toluene), usinga reducing agent (e.g. diisopropyl aluminum hydride) at −78° C.˜50° C.

The reaction of the compound (VI) and the compound after reductivereaction of the compound of formula (I-B-2) is known, for example, it iscarried out in an organic solvent (e.g. dimethylformamide), using a base(e.g. sodium hydride) at 0° C.˜50° C.

The reaction of the compound (VII) and the compound after reductivereaction of the compound of formula (I-B-2) is known, for example, it iscarried out in an organic solvent (e.g. methanol, ethanol, isopropanol)at 0° C.˜100° C.

On the other hand, in the compound of formula (I-B), the compound inwhich R¹ is NR⁴R⁵ and R⁴ and R⁵ each independently, is C1–15 alkyl whichis substituted by 1–5 of R¹⁷ or unsubstituted, and R² and R³ are not OH,cyano, ═N—OR¹¹ or a group containing OH, cyano or ═N—OR¹¹, that is thecompound (I-B-3)

wherein R^(4b-3) and R^(5b-3) each independently, is C1–15 alkyl whichis substituted by 1–5 of R¹⁷ or unsubstituted and the other symbols areas hereinbefore defined;may be also prepared according to following Scheme (1).

In Scheme (1), R^(4b-6) is C1–14 alkyl which is substituted by 1–5 ofR¹⁷ or unsubstituted, R^(5b-4) is C1–14 alkyl which is substituted by1–5 of R¹⁷ or unsubstituted and the other symbols are as hereinbeforedefined.

Amidation reaction is known, for example, it is carried out in anorganic solvent (e.g. chloroform, methylene chloride, diethyl ether,tetrahydrofuran) or without a solvent, using an acyl halide (e.g. oxalylchloride or thionyl chloride etc.) at −20° C.˜reflux temperature, andthen the obtained acyl halide derivative may be reacted with amine, inan organic solvent (e.g. chloroform, methylene chloride, diethyl ether,tetrahydrofuran), in the presence of a tertiary amine (e.g. pyridine,triethyl amine, dimethyl aniline, dimethylaminopyridine) at 0–40° C. Thereaction may be carried out under an inert gas (e.g. argon, nitrogen) toavoid water in order to obtain a preferable result.

Reductive reaction is known, for example, it is carried out in anorganic solvent (e.g. tetrahydrofuran), using a reducing agent (e.g.borane dimethylsulfide complex, lithium aluminum hydride) at 0°C.˜reflux temperature.

The compound of formula (I-B-7) may be prepared by reacting the compoundof formula (II-2)

wherein all symbols are as hereinafter defined;with a compound of formula (III-2)

wherein all symbols are as hereinafter defined;or successively, subjecting to oxidative reaction.

The above reaction of the compound of formula (II-2) and the compound offormula (III-2) is known, for example, it is carried out in an organicsolvent (e.g. benzene, toluene) using an acid (e.g. p-toluenesulfonicacid or hydrate thereof) at from room temperature to reflux temperature,and successively, in an organic solvent (e.g. tetrahydrofuran), usingbase (e.g. lithium isopropylamide) at −10˜50° C.

(C) In the compound of formula (I), the compound in which at least oneof R² and R³ is OH or a group containing OH, that is the compound offormula (I-C)

wherein each Z^(C), U^(C) and R^(3-C) is same meaning as Z, U and R³,with the proviso that at least one of them is OH or a group containingOH and the other symbols are as hereinbefore defined;may be also prepared by subjecting to demethylation of the compound inwhich at least one of R² and R³ is methoxy or a group containing methoxyin the compound of formula (I-B), that is the compound of formula(I-B-8)

wherein each Z^(b-8), U^(b-8) and R^(3-b-8) is same meaning as Z, U andR³, with the proviso that at least one of them is methoxy or a groupcontaining methoxy and the other symbols are as hereinbefore defined.

Demethylation reaction is known, for example, it is carried out in anorganic solvent (e.g. methylene chloride, ethyl acetate, chloroform),using Lewis acid (e.g. boron tribomide), at −80° C.˜80° C.

(D) In the compound of formula (I), the compound in which at least oneof R¹, R² and R³ is a group containing ═N—OR⁶ or ═N—OR¹¹, that is thecompound of formula (I-D)

wherein each R^(1-d), Z^(d), U^(d) and R^(3-d) is same meaning as R¹, Z,U and R³, with the proviso that at least one of them is a groupcontaining ═N—OR⁶ or ═N—OR¹¹ and the other symbols are as hereinbeforedefined;may be prepared

-   (1) by subjecting to deacetalization the compound in which at least    one of R¹, R² and R³ is a group containing —CH(O—C1–4 alkyl)₂ in the    compound of formula (I-B), that is the compound of formula (I-B-9)

wherein each R^(1-b-9), Z^(b-9), U^(b-9) and R^(3-b-9) is same meaningas R¹, Z, U and R³, with the proviso that at least one of them is agroup containing —CH(O—C1–4 alkyl)₂ and the other symbols are ashereinbefore defined;successively, to oxime formation reaction, or

-   (2) by subjecting to oxidative reaction the compound in which    R^(1-a) is a group containing OH in the compound of formula (I-B),    or the compound of formula (I-C), that is the compound of formula    (I-B-10)

wherein each R^(1-b-10), Z^(b-10), U^(b-10) and R^(3-b-10) is samemeaning as R¹, Z, U and R³, with the proviso that R^(1-b-10) is OH or atleast one of Z^(b-10), U^(b-10) and R^(3-b-10) is a group containing OHand the other symbols are as hereinbefore defined;successively, to oxime formation reaction.

Deacetalization reaction is known, for example, it is carried out in anorganic solvent (e.g. acetic acid, dioxane), using an acid (e.g.hydrochloric acid, sulfuric acid) at 0˜100° C.

Oxidative reaction is known, for example, it is carried out in anorganic solvent (e.g. methylene chloride) or without a solvent, in thepresence of a base (e.g. triethylamine, diisopropylethylamine), usingdimethylsulfoxide and sulfur trioxide pyridine complex,dicyclohexylcarbodiimide or oxalyl chloride at 0˜50° C.

Oxime formation reaction is known, for example, it is carried out in anorganic solvent (e.g. pyridine), using H₂N—O—R⁶ or H₂N—O—R¹¹, at 0˜50°C.

(E) In the compound of formula (I), the compound in which at least oneof R¹, R² and R³ is cyano or a group containing cyano, that is thecompound of formula (I-E)

wherein each R^(1-e), Z^(e), U^(e) and R^(3-e) is same meaning as R¹, Z,U and R³, with the proviso that at least one of R^(1-e), Z^(e), U^(e)and R^(3-e) is cyano or a group containing cyano and the other symbolsare as hereinbefore defined;may be prepared by subjecting to dehydration reaction the compound inwhich at least one of R¹, R² and R³ is a group containing ═N—OH in thecompound of formula (I-D), that is the compound of (I-D-1)

wherein each R^(1-d-1), Z^(d-1), U^(d-1) and R^(3-d-1) is same meaningas R¹, Z, U and R³, with the proviso that at least one of R^(1-d-1),Z^(d-1), U^(d-1) and R^(3-d-1) is a group containing ═N—OH and the othersymbols are as hereinbefore defined.

Dehydration reaction is known, for example, it is carried out in anorganic solvent (e.g. methylene chloride), in the presence of a base(e.g. triethylamine, diisopropylethylamine), usingtrifluoromethansulforic acid anhydrous or trichloromethylchlorocarbonate at 0˜50° C.

The compound of formula (IV) may be prepared by subjecting tohalogenation reaction the compound of formula (I-A).

The compounds of formula (II), (III), (V), (VI) and (VII) may be knownper se, or may be prepared by known methods. For example, among thecompound of formula (II)

wherein R^(2-a) is same meaning as R², with the proviso that it is notOH, cyano, ═N—OR¹¹ or a group containing OH, cyano or ═N—OR¹¹, andR^(3-a) is as hereinbefore defined;may be prepared by reacting the compound of formula (VIII)

wherein all symbols are as hereinbefore defined;with hydradine. Besides, in the compound of formula (III),cyclopentanon-2-carboxylic acid ethyl ester is commercially available.In the compound of formula (VI),1-cyano-1-(2-methyl-4-methoxyphenyl)propane-2-one is described in thedocument of Bioorganic & Med. Chem., 8, 181–189 (2000).

And the starting materials and reagents in the present invention may beknown per se or may be prepared by known methods.

In each reaction in the present specification, reaction products may bepurified by conventional purification techniques, e.g. by distillationunder atmospheric or reduced pressure, by high performance liquidchromatography, by thin layer chromatography or by column chromatographyusing silica gel or magnesium silicate; or by washing or byrecrystallization. Purification may be carried out after each reactionor after a series of reactions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a graph of the time spent in the open arms of rats thatwere administered 1, 3, 10 and 30 mg/kg of the present compound.

FIG. 2 shows a graph of the number of entries into the open arms of ratsthat were administered 1, 3, 10 and 30 mg/kg of the present compound.

PHARMACOLOGICAL ACTIVITIES

The compound of the present invention of formula (I) possesses CRFreceptor antagonistic activity, for example, such an effect of thecompound of the present invention was confirmed by following tests.

(1) Binding Assay

[Cell Membrane Preparation]

After the cell line expressing human CRF1 receptor (expressed cell line:CHO-K1 cells) was cultured to reached confluence, the cells wereharvested with a scraper. Harvested cells were washed twice with PBSbefore being suspended in binding assay buffer (Tris-HCl (50 mM, pH7.0), EDTA (2 mM, pH 8.0), MgCl₂ (10 mM)) cooled by ice. Suspended cellswere homogenized with a Downs-type homogenizer and subjected tocentrifugation at 10,000 g to collect the membrane fraction. Theharvested cell membrane fraction was resuspended with a small quantityof the binding assay buffer, and further diluted with said buffer to 1mg/mL. The membrane fraction thus obtained was used for binding assay.

[Binding Assay]

Fifty μL of [¹²⁵I] h/r CRF prepared to 0.5 nM with binding assay bufferwas added to siliconized 1.5 mL tubes. 1 μL of compounds diluted inappropriate multiples, DMSO (for total binding use), or h/r CRF solution(100 μM, for the non-specific binding use), respectively, added to thetubes. Samples of 50 μL each of the membrane fraction preparation wereadded to the tubes to initiate the reaction (final concentration of[¹²⁵I] h/r CRF: 0.25 nM), then the mixtures were incubated for 2 hoursat room temperature. After termination of the reaction, tubes weresubjected to centrifugation at 15,000 g to collect the membranefraction. The supernatant was discarded, and the pellet was rinsed twicewith cooled PBS (−) containing 0.01% Triton X-100. Radioactivity valuesof the respective tubes were measured with a γ-counter.

The specific binding was derived by subtracting the non-specific bindingvalue from the each binding value.

The results indicated that these invented compounds exhibited potentaffinity on CRF1 receptor (IC₅₀: <1 μM).

(2) A Measurement of an Antianxiety Activity Using the ElevatedPlus-Maze

Two arms (open and closed) of equal width and length (50 cm×10 cm),which crossed at a right angle to form a plus maze, were elevated to aheight 50 cm above the ground level. The closed arm had a wall of 40 cm.Lighting on both ends of the open arm was maintained at constantillumination. Thirty minutes after administration of various doses oftest-compounds (5 mL/kg), male SD rats were placed in the center of theplus maze. The time spent(s) in the open arms and the number of entriesinto the respective arms were measured within a 5 minutes period. Theinvestigation personnel for measuring the indexes positioned at a fixedlocation during the course of the experiment.

The result was shown in FIGS. 1 and 2. These figures indicated that thetime spent in the open arms was extend significantly and the number ofentries into the open arms was increased significantly by anadministration of 3 and 10 mg/kg of the compound of Example 2(78) of thepresent invention, that is it was shown an antianxiety effect.

[Toxicity]

The toxicity of the compounds of the present invention is very low andtherefore, it is confirmed that these compounds are safe for use asmedicine.

INDUSTRIAL APPLICABILITY

[Application to Pharmaceuticals]

The compounds of the present invention of the formula (I) are useful, inorder to possess CRF receptor antagonistic activity, for the preventionand/or treatment of diseases induced by extraordinary secretion of CRF,for example, depression, single episode depression, recurrentdepression, postpartum depression, child abuse induced depression,anxiety, anxiety related disorders (e.g. panic disorder, particularphobia, fear of falling, social phobia, obsessive compulsive disorder),emotional disorder, bipolar disorder, posttraumatic stress disorder,peptic ulcer, diarrhea, constipation, irritable bowl syndrome,inflammatory bowel disease (ulcerative colitis, Crohn's disease),stress-induced gastrointestinal disturbance, nervous emesis, eatingdisorder (e.g. anorexia nervosa, bulimia nervosa), obesity,stress-induced sleep disorder, pain of muscular fiber induced sleepdisorder, stress-induced immune suppression, stress-induced headache,stress-induced fever, stress-induced pain, post operative stress,rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis, thyroiddysfunction, uveitis, asthma, inappropriate anti-diarrhea hormoneinduced disorder, pain, inflammation, allergic disease, head injury,spinal cord injury, ischemic neuron injury, toxicity neuron injury,Cushing's disease, seizure, spasm, muscular spasm, epilepsy, ischemicdisease, Parkinson's disease, Huntington disease, urinary incontinence,Alzheimer's disease, senile dementia of Alzheimer type, multi-infarctdementia, amyotrophic lateral sclerosis, hypoglycemia, cardiovascular orheart-related disease (hypertension, tachycardia, congestive heartfailure), drug addiction or alcohol dependence syndrome.

For the purpose described above, the compounds of formula (I) of thepresent invention, non-toxic salts thereof, an acid addition saltsthereof or hydrates thereof may be normally administered systemically ortopically, usually by oral or parenteral administration.

The doses to be administered are determined depending upon, for example,age, body weight, symptom, the desired therapeutic effect, the route ofadministration, and the duration of the treatment, etc. In the humanadult, the doses per person at a time are generally from 1 mg to 1000mg, by oral administration, up to several times per day, and from 0.1 mgto 100 mg, by parenteral administration, preferably intravenousadministration, up to several times per day, or continuousadministration between 1 and 24 hours per day into vein.

As mentioned above, the doses to be used depend upon various conditions.Therefore, there are cases wherein doses lower than or greater than theranges specified above may be used.

The compounds of the present invention may be administered in the formof, for example, solid compositions, liquid compositions or othercompositions for oral administration, injections, liniments orsuppositories for parenteral administration.

Solid compositions for oral administration include compressed tablets,pills, capsules, dispersible powders and granules. Capsules include hardcapsules and soft capsules.

In such solid forms, one or more of the active compound(s) may beadmixed with vehicles, such as lactose, mannitol, glucose,microcrystalline cellulose, starch; binders, such as hydroxypropylcellulose, polyvinylpyrrolidone or magnesium metasilicate aluminate;disintegrants, such as cellulose calcium glycolate; lubricants, such asmagnesium stearate; stabilizing agents, and solution adjuvants, such asglutamic acid or aspartic acid; and prepared according to methods wellknown in normal pharmaceutical practice. The solid forms may, ifdesired, be coated with coating agents, such as sugar, gelatin,hydroxypropyl cellulose or hydroxypropylmethyl cellulose phthalate; orbe coated with two or more films. And further, coating may includecontainment within capsules of absorbable materials such as gelatin.

Liquid forms for oral administration include pharmaceutically acceptablesolutions, suspensions and emulsions, syrups and elixirs. In such forms,one or more of the active compound(s) may be dissolved, suspended oremulsified into diluent(s) commonly used in the art, such as purifiedwater, ethanol or a mixture thereof. Besides such liquid forms may alsocomprise some additives, such as wetting agents, suspending agents,emulsifying agents, sweetening agents, flavoring agents, aroma,preservative or buffering agent.

Injections for parenteral administration include sterile aqueous,suspensions, emulsions and solid forms that are dissolved or suspendedinto solvent(s) for injection immediately before use. In injections, oneor more of the active compound(s) may be dissolved, suspended oremulsified into solvent(s). The solvents may include distilled water forinjection, physiological salt solution, vegetable oil, propylene glycol,polyethylene glycol, alcohol, e.g. ethanol, or a mixture thereof.Injections may comprise some additives, such as stabilizing agents,solution adjuvants, such as glutamic acid, aspartic acid orPOLYSORBATE80 (registered trade mark); suspending agents, emulsifyingagents, soothing agent, buffering agents, preservative. They may besterilized at a final step, or may be prepared and compensated accordingto sterile methods. They may also be manufactured in the form of sterilesolid forms, for example, freeze-dried products, which may be dissolvedin sterile water or some other sterile diluent(s) for injectionimmediately before use.

Other forms for parenteral administration include liquids for externaluse, ointments and endermic liniments, inhalations, sprays,suppositories and pessaries for vaginal administration which compriseone or more of the active compound(s) and may be prepared by methodsknown per se. Sprays may comprise additional substances other thandiluents, such as stabilizing agents, such as sodium sulfate; isotonicbuffers, such as sodium chloride, sodium citrate or citric acid. Forpreparation of such sprays, for example, the method described in theU.S. Pat. No. 2,868,691 or U.S. Pat. No. 3,095,355 may be used.

BEST MODE FOR CARRYING OUT THE INVENTION

The following reference examples and examples illustrate, but do notlimit the present invention.

The solvents in parenthesis show the developing or eluting solvents andthe ratios of the solvents used are by volume in chromatographicseparations and TLC.

The NMR data are shown with the solvent used in the measurements, inparentheses.

REFERENCE EXAMPLE 1 2-methyl-4-methoxyphenylacetonitrile

Under argon atmosphere, a mixture of N-bromosuccinimide (17.8 g) and2,2′-azobisisobutyronitrile (492 mg) was added to a solution of1,2-dimethyl-4-methoxybenzene (13.6 g) in carbon tetrachloride (200 ml).The mixture was refluxed for 6.5 hours. The reaction mixture was cooledwith ice-bath. An insoluble matter was removed by filtration, and washedwith carbon tetrachloride. A combined filtrate was concentrated. Theresidue was dissolved into N,N-dimethylformamide (100 ml) and sodiumcyanide (9.86 g) was added to the mixture. The mixture was stirred overnight at room temperature. The reaction mixture was poured into water,and the mixture was extracted with diethyl ether. The organic layer waswashed with a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (ethyl acetate:n-hexane=1:6→1:4)to give the title compound (11.78 g) having the following physical data.

TLC: Rf 0.20 (n-hexane:ethyl acetate=9:1);

NMR (300 MHz, CDCl₃): δ 7.24 (d, J=8.0 Hz, 1H), 6.78–6.72 (m, 2H), 3.79(s, 3H), 3.60 (s, 2H), 2.32 (s, 3H).

REFERENCE EXAMPLE 2 1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one

Under argon atmosphere, to a solution of the compound prepared inreference example 1 (11.7 g) in ethyl acetate (60 ml), metallic sodium(2.3 g) was added in numbers. The mixture was stirred for 2 hours at 50°C. Ethyl acetate (40 ml) was added to the reaction mixture, and themixture was refluxed for 2.5 hours and then it was stirred overnight atroom temperature. A precipitation matter was collected by filtration,and it was washed with diethyl ether. The obtained crystal was dissolvedinto water (300 ml). The solution was adjusted pH 4 by adding 2Nhydrochloric acid, and extracted with ethyl acetate. The organic layerwas dried over anhydrous sodium sulfate and concentrated to give thetitle compound (12.06 g) having the following physical data.

TLC: Rf 0.45 (n-hexane:ethyl acetate=1:1).

REFERENCE EXAMPLE 3 2-chloro-4-methoxyboronic acid

A solution of 3-chloro-4-bromoanisole (2.14 g) in anhydroustetrahydrofuran (10 ml) was cooled at −78° C. 1.56 M n-butyllithium/hexane (6.5 ml) was dropped into the solution, and the mixturewas stirred for 30 minutes. Triisopropyl borate (2.3 ml) was droppedinto the reaction mixture, and the mixture was stirred for 2 hours at−78° C. A saturated aqueous solution of ammonium chloride was added tothe reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated. Aobtained solid was washed with t-butyl methyl ether (4 ml), filtered anddried over to give the title compound (681 mg) having the followingphysical data.

TLC: Rf 0.55 (methylene chloride:methanol=19:1);

NMR (300 MHz, CDCl₃): δ 7.22 (d, J=8.4 Hz, 1H), 6.93 (d; J=2.4 Hz, 1H),6.86 (dd, J=8.4, 2.4 Hz, 1H), 3.79 (s, 3H).

REFERENCE EXAMPLE 4 4-(2-chloro-4-methoxyphenyl)-5-methylisoxazole

To a suspension of the compound prepared in reference example 3 (644mg), 4-iodo-5-methylisoxazole (658 mg) and sodium bicarbonate (791 mg)in dimethoxyethane (2.5 ml)/water (2.5 ml),tetrakis(triphenylphosphine)palladium (36 mg) was added. The mixture wasstirred for 16 hours at 80° C. To the reaction mixture that was cooledto room temperature, water and ethyl acetate were added. An insolublematter was removed by filtration. An organic layer was separated fromfiltrate, it was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(n-hexane:ethyl acetate=19:1→15:1) to give the title compound (637 mg)having the following physical data.

TLC: Rf 0.44 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.29 (brs, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.04 (d,J=2.4 Hz, 1H), 6.87 (dd, J=8.4, 2.4 Hz, 1H), 3.84 (s, 3H), 2.41 (brs,3H).

REFERENCE EXAMPLE 5 1-cyano-1-(2-chloro-4-methoxyphenyl)propan-2-one

To a solution of the compound prepared in reference example 4 (623 mg)in methanol (2.8 ml), 1.5M sodium methoxide/methanol (2.8 ml) was added,and the mixture was stirred for 4 hours. The reaction mixture wasdiluted with water, and washed with hexane/t-butyl methyl ether (10 ml;1:1). A water layer was adjusted pH 5 by adding 4N Hydrochloric acid (1ml), and extracted with ethyl acetate. The organic layer was washed witha saturated aqueous solution of sodium bicarbonate and a saturatedaqueous solution of sodium chloride, dried over anhydrous magnesiumsulfate and concentrated to give the title compound (497 mg) having thefollowing physical data.

TLC: Rf 0.13 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.38 (d, J=8.4 Hz, 1H), 7.00 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 5.11 (s, 1H), 3.83 (s, 3H), 2.29 (s, 3H).

REFERENCE EXAMPLE 65-amino-3-methyl-4-(2-methyl-4-methoxyphenyl)pyrazole

To a solution of the compound prepared in reference example 2 (8.63 g)in toluene (200 ml), acetic acid (8.0 ml) and hydrazine one hydrate (4.5ml) were added. The mixture was refluxed for 5.5 hours and stirredovernight at room temperature. The reaction mixture was concentrated. 6NHydrochloric acid was added to a residue, and the solution was extractedwith ethyl acetate/n-hexane (30 ml/30 ml). A water layer was basified byadding concentrated aqueous ammonia, and extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate andconcentrated to give the title compound (8.38 g) having the followingphysical data.

TLC: Rf 0.30 (chloroform:methanol=9:1);

NMR (300 MHz, CDCl₃): δ 7.08 (d, J=8.0 Hz, 1H), 6.84 (d, J=2.5 Hz, 1H),6.77 (dd, J=8.0, 2.5 Hz, 1H), 4.10 (brs, 3H), 3.83 (s, 3H), 2.18 (s,3H), 2.07 (s, 3H).

EXAMPLE 18-hydroxy-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in reference example 6 (500 mg)in acetic acid (3 ml), ethyl cyclopentanone-2-carboxylate (0.40 ml) wasadded. And the mixture was refluxed for 3 hours. After the reactionmixture was cooled to room temperature, diethyl ether/n-hexane (10 ml;2:1) was added to the mixture. A precipitated crystal was collected byfiltration, and the crystal was washed with diethyl ether/n-hexane (10ml; 2:1), dried over to give the title compound (480 mg) having thefollowing physical data.

TLC: Rf 0.47 (chloroform:methanol=9:1);

NMR (300 MHz, DMSO-d₆): δ 11.90 (brs, 1H), 7.10 (d, J=8.0 Hz, 1H), 6.93(d, J=3.0 Hz, 1H), 6.83 (dd, J=8.0, 3.0 Hz, 1H), 3.78 (s, 3H), 2.81 (t,J=7.5 Hz, 2H), 2.66 (t, J=7.5 Hz, 2H), 2.07 (s, 3H), 2.05 (s, 3H), 2.03(m, 2H).

REFERENCE EXAMPLE 78-chloro-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a suspension of the compound prepared in Example 1 (400 mg) intoluene (4 ml), phosphorus oxychloride (0.60 ml) and diethylaniline(0.25 ml) were added. The mixture was refluxed for 1 hour. The reactionmixture was cooled, and it was poured into a cooled aqueous solution ofsodium bicarbonate. The mixture was stirred for 10 minutes to degradeexcess of phosphorus oxychloride. The reaction mixture was extractedwith ethyl acetate. The organic layer was washed with a saturatedaqueous solution of sodium chloride, dried over anhydrous sodium sulfateand concentrated. The residue was purified by column chromatography onsilica gel (ethyl acetate: n-hexane=1:3→1:2) to give the title compound(411 mg) having the following physical data.

TLC: Rf 0.52 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.5 Hz, 1H), 6.88 (d, J=2.5 Hz, 1H),6.81 (dd, J=8.5, 2.5 Hz, 1H), 3.83 (s, 3H), 3.09–3.00 (m, 4H), 2.40 (s,3H), 2.23 (m, 2H), 2.15 (s, 3H).

EXAMPLE 28-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

A mixture of the compound prepared in reference example 7 (150 mg) and3-pentylamine (0.6 ml) was stirred for 1 hour at 140° C. The reactionmixture was cooled and purified by column chromatography on silica gel(ethyl acetate:n-hexane=1:3) to give the title compound (169 mg) havingthe following physical data.

TLC: Rf 0.57 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.5 Hz, 1H), 6.85 (d, J=3.0 Hz, 1H),6.78 (dd, J=8.5, 3.0 Hz, 1H), 6.21 (d, J=10.5 Hz, 1H), 3.82 (s, 3H),3.81 (m, 1H), 3.08 (t, J=7.0 Hz, 2H), 2.89 (t, J=8.0 Hz, 2H), 2.30 (s,3H), 2.19 (s, 3H), 2.14 (m, 2H), 1.69 (m 4H), 1.02 (m, 6H).

EXAMPLE 2(1)–2(365)

The following compounds were obtained, using a corresponding compound instead of 1,2-dimethyl-4-methoxybenzene, by the same procedure as aseries of reactions of Reference example 1→Reference example 2→Referenceexample 6→Example 1 using a corresponding compound in stead of ethylcyclopentanone-2-carboxylate→Reference example 7→Example 2 using acorresponding compound in stead of 3-pentylamine, or using the compoundprepared in Reference example 5 or a corresponding compound, by the sameprocedure as a series of reactions of Reference example 6→Example1→Reference example 7→Example 2, or successively by a known method to bea salt of compound.

EXAMPLE 2(1)8-(N-ethyl-N-n-butylamino)-2-methoxymethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.43 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.22 (d, J=8.7 Hz, 1H), 6.84 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.7, 2.7 Hz, 1H), 4.49 (m, 2H), 3.81 (s, 3H), 3.67 (q, J=7.2Hz, 2H), 3.61 (t, J=7.2 Hz, 2H), 3.33 (s, 3H), 2.97 (t, J=7.2 Hz, 2H),2.91 (t, J=7.8 Hz, 2H), 2.19 (s, 3H), 2.13 (m, 2H), 1.55 (m, 2H), 1.35(m, 2H), 1.17 (t, J=7.2 Hz, 3H), 0.89 (t, J=7.2 Hz, 3H).

EXAMPLE 2(2)8-(N-propyl-N-(2-hydroxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.80 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.4, 2.7 Hz, 1H), 3.90 (t, J=4.8 Hz, 2H), 3.83 (s, 3H), 3.64(m, 2H), 3.43 (m, 2H), 2.98 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.8 Hz, 2H),2.31 (s, 3H), 2.17 (s, 3H), 2.15 (m, 2H), 1.58 (m, 2H), 0.95 (t, J=7.2Hz, 3H).

EXAMPLE 2(3)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydrothieno[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.51 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.5 Hz, 1H), 6.86 (d, J=2.5 Hz, 1H),6.79 (dd, J=8.5, 2.5 Hz, 1H), 6.44 (d, J=10.0 Hz, 1H), 4.32 (brs, 2H),4.14 (brs, 2H), 3.82 (s, 3H), 3.76 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H),1.84–1.57 (m 4H), 1.03 (t, J=7.0 Hz, 6H).

EXAMPLE 2(4)9-(3-pentylamino)-6-methyl-5-(2-methyl-4-methoxyphenyl)-2,3-dihydrothieno[3,2-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.5 Hz, 1H), 6.85 (d, J=3.0 Hz, 1H),6.79 (dd, J=8.5, 3.0 Hz, 1H), 6.17 (d, J=10.0 Hz, 1H), 3.99 (m, 1H),3.82 (s, 3H), 3.36–3.20 (m, 4H), 2.30 (s, 3H), 2.18 (s, 3H), 1.82–1.56(m 4H), 1.03 (t, J=7.5 Hz, 6H).

EXAMPLE 2(5)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.5 Hz, 1H), 6.86 (d, J=2.5 Hz, 1H),6.79 (dd, J=8.5, 2.5 Hz, 1H), 6.32 (d, J=10.0 Hz, 1H), 5.29 (s, 2H),4.90 (brs, 2H), 3.82 (s, 3H), 3.24 (m, 1H), 2.33 (s, 3H), 2.18 (s, 3H),1.84–1.56 (m 4H), 1.02 (t, J=7.5 Hz, 6H).

EXAMPLE 2(6)9-(3-pentylamino)-6-methyl-5-(2-methyl-4-methoxyphenyl)-2,3-dihydro-furo[3,2-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.43 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (brs, 1H), 7.12 (d, J=8.4 Hz, 1H), 6.89 (d,J=2.7 Hz, 1H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 4.76 (t, J=9.0 Hz, 2H),4.30 (m, 1H), 3.83 (s, 3H), 3.74 (t, J=9.0 Hz, 2H), 2.34 (s, 3H), 2.19(s, 3H), 1.90–1.70 (m, 4H), 1.04 (m, 6H).

EXAMPLE 2(7)9-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,6,7,8-tetrahydro-pyrazolo[3,2-b]quinazolinehydrochloride

TLC: Rf 0.45 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 13.04 (brs, 1H), 7.91 (brs, 1H), 7.15 (d, J=8.5Hz, 1H), 6.96 (d, J=2.5 Hz, 1H), 6.87 (dd, J=8.5, 2.5 Hz, 1H), 5.65(brs, 1H), 3.79 (s, 3H), 2.75 (m, 2H), 2.58 (m, 2H), 2.19 (s, 3H), 2.05(s, 3H), 1.88–1.64 (m, 8H), 0.91 (t, J=7.5 Hz, 6H).

EXAMPLE 2(8) 6-methyl-5-(2-methyl-4-methoxyphenyl)-9-[(2S,4R)-4-methoxy-2-methoxymethylpyrolidin-1-yl]-2,3-dihydro-furo[3,2-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.24 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, DMSO-d₆): δ 7.09 (d, J=7.5 Hz, 1H), 6.90 (d, J=2.4 Hz,1H), 6.81 (dd, J=7.5, 2.4 Hz, 1H), 5.07 (brs, 1H), 4.66 (dt, J=9.0, 9.0Hz, 1H), 4.56 (dt, J=9.0, 9.0 Hz, 1H), 4.24 (dd, J=12.6, 3.6 Hz, 1H),4.05 (brs, 1H), 3.85 (d, J=12.6 Hz, 1H), 3.77 (s, 3H), 3.42 (dd, J=10.2,3.9 Hz, 1H), 3.33 (dd, J=10.2, 5.1 Hz, 1H), 3.22 (dd, J=9.0, 9.0 Hz,2H), 3.21 (s, 3H), 3.18 (s, 3H), 2.18 (s, 3H), 2.07 (s, 3H), 2.30–1.95(m, 2H).

EXAMPLE 2(9)9-(3-pentylamino)-6-methyl-5-(2-methyl-4-methoxyphenyl)-2,3-dihydropyrrolo[3,2-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.37 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=2.7, 8.4 Hz, 1H), 5.86 (d, J=10.5 Hz, 1H), 4.07 (m, 1H),3.82 (s, 3H), 3.58 (t, J=8.1 Hz, 2H), 3.06 (t, J=8.1 Hz, 2H), 2.30 (s,3H), 2.19 (s, 3H), 1.52–1.82 (m, 4H), 1.01 (m, 6H).

EXAMPLE 2(10) 2-methyl-3-(2-methyl-4-methoxyphenyl)-8-[(2S,4R)-4-methoxy-2-methoxymethylpyrolidin-1-yl]-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.30 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 and 7.07 (d, J=8.4 Hz, two conformers, 1H),6.89 and 6.87 (d, J=2.7 Hz, two conformers, 1H), 6.83 and 6.80 (dd,J=8.4, 2.7 Hz, two conformers, 1H), 5.65 (brs, 1H), 4.32–4.10 (m, 3H),3.82 (s, 3H), 3.50–3.40 (m, 4H), 3.367 and 3.361 (s, two conformers,3H), 3.29 and 3.28 (s, two conformers, 3H), 3.23–2.99 (m, 2H), 2.42 (m,1H), 2.30–2.10 (m, 3H), 2.245 and 2.240 (s, two conformers, 3H), 2.22and 2.14 (s, two conformers, 3H).

EXAMPLE 2(11) 2-methyl-3-(2-methyl-4-methoxyphenyl)-8-[(2S,4R)-4-methoxy-2-methoxymethylpyrolidin-1-yl]-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.22 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, DMSO-d₆) 7.10 (brs, 1H), 6.89 (d, J=2.4 Hz, 1H), 6.81 (dd,J=8.1, 2.4 Hz, 1H), 5.33 (d, J=10.8 Hz, 1H), 5.25 (brs, 1H), 5.15 (d,J=10.8 Hz, 1H), 4.85 (d, J=14.4 Hz, 1H), 4.75 (d, J=14.4 Hz, 1H),4.10–3.85 (m, 3H), 3.77 (s, 3H), 3.39 (dd, J=9.9, 4.5 Hz, 1H), 3.28 (dd,J=9.9, 5.1 Hz, 1H), 3.22 (s, 3H), 3.15 (s, 3H), 2.25 (m, 1H), 2.21 (s,3H), 2.15–2.00 (m, 4H).

EXAMPLE 2(12) 6-methyl-5-(2-methyl-4-methoxyphenyl)-9-[(2S,4R)-4-methoxy-2-methoxymethylpyrolidin-1-yl]-2,3-dihydro-pyrrolo[3,2-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.43 (chloroform:methanol=20:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=2.7, 8.4 Hz, 1H), 4.71 (m, 1H), 4.20 (m, 1H), 4.06 (m, 1H),3.82 (s, 3H), 3.60 (t, J=7.8 Hz, 2H), 3.54 (m, 1H), 3.48 (dd, J=4.5, 9.6Hz, 1H), 3.39 (m, 1H), 3.34 (s, 3H), 3.28 (s, 3H), 3.09 (m, 2H),2.24–2.40 (m, 4H), 2.18 (s, 3H), 2.01 (m, 1H).

EXAMPLE 2(13)8-isopropylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.34 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.4, 2.7 Hz, 1H), 6.39 (d, J=9.6 Hz, 1H), 5.32 (s, 2H), 4.90(s, 2H), 3.82 (s, 3H), 3.74 (m, 1H), 2.32 (s, 3H), 2.16 (s, 3H), 1.41(d, J=6.6 Hz, 6H).

EXAMPLE 2(14)8-[(2S)-1,1-dimethoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.26 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H),6.79 (dd, J=8.1, 2.4 Hz, 1H), 6.57 (brd, J=11.1 Hz, 1H), 5.36 (d, J=9.9Hz, 1H), 5.26 (d, J=9.9 Hz, 1H), 4.90 (s, 2H), 4.33 (d, J=3.9 Hz, 1H),3.82 (s, 3H), 3.50 (s, 3H), 3.48 (s, 3H), 3.39 (m, 1H), 2.32 (s, 3H),2.17 (s, 3H), 1.88 (m, 1H), 1.68 (m, 1H), 1.04 (brs, 3H).

EXAMPLE 2(15)8-[(2S)-1,1-dimethoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.85 (d, J=3.0 Hz, 1H),6.77 (dd, J=8.1, 3.0 Hz, 1H), 6.47 (brd, J=11.8 Hz, 1H), 4.34 (brs, 1H),4.01 (m, 1H), 3.81 (s, 3H), 3.49 (s, 6H), 3.19–3.00 (m, 2H), 2.89 (t,J=7.8 Hz, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.86 (m, 1H),1.65 (m, 1H), 1.04 (brs, 3H).

EXAMPLE 2(16)8-(1,3-dimethoxypropan-2-yl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.42 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.87 (brd, J=8.1 Hz,1H), 6.85 (d, J=2.4 Hz, 1H), 6.79 (dd, J=8.1, 2.4 Hz, 1H), 5.33 (s, 2H),4.89 (s, 2H), 3.81 (s, 3H), 3.75 (m, 1H), 3.62 (d, J=4.8 Hz, 4H), 3.42(s, 6H), 2.33 (s, 3H), 2.16 (s, 3H).

EXAMPLE 2(17)8-bis(2-methoxyethyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.24 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.1, 2.7 Hz, 1H), 5.22 (s, 2H), 4.89 (s, 2H), 3.88 (t, J=6.0Hz, 4H), 3.82 (s, 3H), 3.55 (t, J=6.0 Hz, 4H), 3.30 (s, 6H), 2.33 (s,3H), 2.16 (s, 3H).

EXAMPLE 2(18)8-(1,3-dimethoxypropan-2-yl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.01 (d, J=8.4 Hz, 1H), 6.72 (d, J=2.7 Hz, 1H),6.64 (dd, J=8.4, 2.7 Hz, 1H), 6.60 (d, J=9.9 Hz, 1H), 4.14 (m, 1H), 3.69(s, 3H), 3.50 (d, J=5.4 Hz, 4H), 3.30 (s, 6H), 2.99 (t, J=7.2 Hz, 2H),2.76 (t, J=7.8 Hz, 2H), 2.18 (s, 3H), 2.04 (s, 3H), 2.01 (m, 2H).

EXAMPLE 2(19)8-bis(2-methoxyethyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.41 (n-hexane ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.4, 2.7 Hz, 1H), 3.88 (t, J=5.7 Hz, 4H), 3.82 (s, 3H), 3.52(t, J=5.7 Hz, 4H), 3.30 (s, 6H), 3.00 (t, J=6.9 Hz, 2H), 2.91 (t, J=7.8Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.14 (m, 2H).

EXAMPLE 2(20)(5RS)-8-(3-pentylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.44 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, DMSO-d₆): δ 8.71 (brs, 1H), 7.15 (d, J=8.5 Hz, 1H), 6.93(d, J=2.5 Hz, 1H), 6.85 (dd, J=8.5, 2.5 Hz, 1H), 5.70 (brs, 1H), 5.25(dd, J=10.0, 2.0 Hz, 1H), 5.17 (d, J=10.0 Hz, 1H), 5.11 (m, 1H), 3.79(s, 3H), 3.26 (m, 1H), 2.26 (s, 3H), 2.10 (s, 3H), 1.83–1.57 (m 4H),1.41 (d, J=5.5 Hz, 3H), 0.93–0.83 (m, 6H).

EXAMPLE 2(21)8-(3-pentylamino)-2-methyl-3-(2,4-dichlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.50 (d, J=2.0 Hz, 1H), 7.35 (d, J=8.5 Hz, 1H),7.29 (dd, J=8.5, 2.0 Hz, 1H), 6.23 (d, J=10.5 Hz, 1H), 3.81 (m, 1H),3.09 (t, J=7.5 Hz, 2H), 2.91 (t, J=7.5 Hz, 2H), 2.34 (s, 3H), 2.15 (m,2H), 1.82–1.55 (m 4H), 1.01 (t, J=7.5 Hz, 6H).

EXAMPLE 2(22)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydropyrrolo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (chloroform:methanol=10:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1H, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=2.7, 8.1 Hz, 1H), 6.29 (d, J=10.2 Hz, 1H), 4.43 (s, 2H),4.10 (s, 2H), 3.82 (s, 3H), 3.49 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H),1.55–1.84 (m, 4H), 1.02 (m, 6H).

EXAMPLE 2(23)8-diethylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.67 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.4, 2.7 Hz, 1H), 3.82 (s, 3H), 3.66 (q, J=7.2 Hz, 4H), 2.99(t, J=7.5 Hz, 2H), 2.91 (t, J=7.5 Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H),2.13 (m, 2H), 1.18 (t, J=7.2 Hz, 6H).

EXAMPLE 2(24)8-(N-ethyl-N-n-butylamino)-2-methyl-3-(2,4-dichlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.78 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.4 Hz, 1H), 6.86 (d, J=3.0 Hz, 1H),6.79 (dd, J=8.4, 3.0 Hz, 1H), 3.82 (s, 3H), 3.70–3.56 (m, 4H), 2.97 (t,J=6.9 Hz, 2H), 2.91 (t, J=7.7 Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H), 2.13(m, 2H), 1.55 (m, 2H), 1.32 (m, 2H), 1.17 (t, J=7.2 Hz, 3H), 0.90 (t,J=7.2 Hz, 3H).

EXAMPLE 2(25)8-dicyclopropylmethylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.1, 2.7 Hz, 1H), 6.36 (d, J=10.2 Hz, 1H), 3.82 (s, 3H),3.41 (m, 1H), 3.01 (t, J=7.2 Hz, 2H), 2.87 (t, J=8.1 Hz, 2H), 2.31 (s,3H), 2.19 (s, 3H), 2.10 (m, 2H), 1.20–1.08 (m, 2H), 0.66–0.32 (m, 8H).

EXAMPLE 2(26)8-(N-propyl-N-(2-hydroxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.26 (n-hexane:ethyl acetate=1:2);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.4 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.80 (dd, J=8.4, 2.7 Hz, 1H), 6.54 (brs, 1H), 5.21 (s, 2H), 4.89 (s,2H), 3.96 (brt, J=4.8 Hz, 2H), 3.83 (s, 3H), 3.80 (m, 2H), 3.29 (t,J=7.5 Hz, 2H), 2.33 (s, 3H), 2.17 (s, 3H), 1.63 (m, 2H), 1.00 (t, J=7.5Hz, 3H).

EXAMPLE 2(27)8-(3-pentylamino)-2-methoxymethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.27 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.19 (d, J=8.5 Hz, 1H), 6.85 (d, J=2.5 Hz, 1H),6.78 (dd, J=8.5, 2.5 Hz, 1H), 6.32 (d, J=10.5 Hz, 1H), 4.54–4.40 (m,2H), 3.82 (s, 3H), 3.81 (m, 1H), 3.37 (s, 3H), 3.10 (t, J=7.0 Hz, 2H),2.91 (t, J=8.0 Hz, 2H), 2.20 (s, 3H), 2.14 (m, 2H), 1.80–1.53 (m, 4H),1.08–0.94 (m, 6H).

EXAMPLE 2(28)8-(3-pentylamino)-2-methyl-3-(1,3-dioxaindan-5-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.22 (d, J=1.5 Hz, 1H), 7.10 (dd, J=1.5, 8.1 Hz,1H), 6.89 (d, J=8.1 Hz, 1H), 6.20 (br d, J=10.5 Hz, 1H), 5.96 (s, 2H),3.80 (m, 1H), 3.08 (t, J=7.5 Hz, 2H), 2.94 (t, J=8.1 Hz, 2H), 2.52 (s,3H), 2.15 (m, 2H), 1.51–1.80 (m, 4H), 1.00 (t, J=7.5 Hz, 6H).

EXAMPLE 2(29)8-(3-pentylamino)-2-methyl-3-(3,4-dimethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.56 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=2.1 Hz, 1H), 7.19 (dd, J=2.1, 8.1 Hz,1H), 6.96 (d, J=8.1 Hz, 1H), 6.20 (br d, J=10.5 Hz, 1H), 3.93 (s, 3H),3.91 (s, 3H), 3.80 (m, 1H), 3.09 (t, J=7.2 Hz, 2H), 2.94 (t, J=7.5 Hz,2H), 2.55 (s, 3H), 2.16 (m, 2H), 1.53–1.81 (m, 4H), 1.00 (t, J=7.2 Hz,6H).

EXAMPLE 2(30)8-cyclopropylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (n-hexane:ethyl acetate=3:2);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.1, 2.7 Hz, 1H), 6.62 (brs, 1H), 5.54 (brs, 2H), 4.91 (brs,2H), 3.82 (s, 3H), 2.89 (m, 1H), 2.30 (s, 3H), 2.15 (s, 3H), 0.98–0.84(m, 4H).

EXAMPLE 2(31)8-(3-pentylamino)-2-cyclobutyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.62 (benzene:ethyl acetate=5:1);

NMR (300 MHz, CDCl₃): δ 7.09 (d, J=8.1 Hz, 1H), 6.83 (d, J=2.7 Hz, 1H),6.75 (dd, J=8.1, 2.7 Hz, 1H), 6.35 (d, J=10.5 Hz, 1H), 3.82 (s, 3H),3.81 (m, 1H), 3.53 (m, 1H), 3.08 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.8 Hz,2H), 2.41 (m, 2H), 2.28–2.06 (m, 4H), 2.15 (s, 3H), 2.01–1.58 (m, 6H),1.05 (t, J=7.5 Hz, 3H), 1.02 (t, J=7.8 Hz, 3H).

EXAMPLE 2(32)8-(3-pentylamino)-2-ethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.59 (benzene:ethyl acetate=5:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.1, 2.7 Hz, 1H), 6.27 (d, J=10.5 Hz, 1H), 3.82 (s, 3H),3.80 (m, 1H), 3.08 (t, J=7.5 Hz, 2H), 2.89 (t, J=7.8 Hz, 2H), 2.67 (m,2H), 2.17 (s, 3H), 2.13 (m, 2H), 1.81–1.52 (m, 4H), 1.16 (t, J=7.2 Hz,3H), 1.04 (t, J=7.5 Hz, 3H), 1.01 (t, J=7.8 Hz, 3H).

EXAMPLE 2(33)8-(3-pentylamino)-2-isopropyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.60 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.28 (m, 1H), 7.09 (d, J=8.4 Hz, 1H), 6.90 (d,J=2.4 Hz, 1H), 6.81 (dd, J=8.4, 2.4 Hz, 1H), 3.99 (m, 1H), 3.84 (s, 3H),3.49 (m, 2H), 3.12 (t, J=7.2 Hz, 2H), 2.99 (m, 1H), 2.28 (m, 2H), 2.20(s, 3H), 1.85 (m, 2H), 1.74 (m, 2H), 1.24 (d, J=6.9 Hz, 3H), 1.19 (d,J=7.2 Hz, 3H), 1.08 (t, J=7.5 Hz, 3H), 1.06 (t, J=7.5 Hz, 3H).

EXAMPLE 2(34)8-(2-ethylbutylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.55 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.46 (m, 1H), 7.11 (d, J=8.4 Hz, 1H), 6.89 (d,J=2.4 Hz, 1H), 6.82 (dd, J=8.4, 2.4 Hz, 1H), 3.83 (s, 3H), 3.74 (t,J=6.0 Hz, 2H), 3.49 (t, J=7.8 Hz, 2H), 3.21 (t, J=7.5 Hz, 2H), 2.28 (s,3H), 2.26 (m, 2H), 2.19 (s, 3H), 1.68 (m, 1H), 1.53 (m, 4H), 1.00 (t,J=7.5 Hz, 6H).

EXAMPLE 2(35)8-(3-pentylamino)-2-methylthiomethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.31 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.31 (brd, J=10.8 Hz, 1H), 7.16 (d, J=8.4 Hz,1H), 6.89 (d, J=2.4 Hz, 1H), 6.80 (dd, J=8.4, 2.4 Hz, 1H), 4.00 (brs,1H), 3.83 (s, 3H), 3.70 (d, J=13.5 Hz, 1H), 3.60 (d, J=13.5 Hz, 1H),3.50 (m, 2H), 3.14 (t, J=7.2 Hz, 2H), 2.29 (m, 2H), 2.32 (s, 3H), 2.04(s, 3H), 1.95–1.65 (m, 4H), 1.07 (t, J=7.2 Hz, 3H), 1.05 (t, J=7.5 Hz,3H).

EXAMPLE 2(36)8-(N-methyl-N-cyclopropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.16 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.1, 2.7 Hz, 1H), 5.47 (brs, 2H), 4.90 (brs, 2H), 3.82 (s,3H), 3.45 (s, 3H), 2.80 (m, 1H), 2.33 (s, 3H), 2.16 (s, 3H), 0.84 (d,J=6.0 Hz, 4H).

EXAMPLE 2(37)8-(3-pentylamino)-2-methyl-3-(2,4-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.13 (d, J=7.5 Hz, 1H), 7.11 (brs, 1H), 7.03 (m,1H), 6.21 (d, J=10.8 Hz, 1H), 3.80 (m, 1H), 3.08 (t, J=6.9 Hz, 2H), 2.89(t, J=7.5 Hz, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 2.13 (m,2H), 1.56–1.82 (m, 4H), 1.02 (m, 6H).

EXAMPLE 2(38)8-(3-pentylamino)-2-methyl-3-(2,5-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.54 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.31 (br d, J=10.2 Hz, 1H), 7.24 (d, J=7.5 Hz,1H), 7.15 (br dd, J=1.2, 7.5 Hz, 1H), 7.01 (brs, 1H), 3.99 (m, 1H), 3.49(t, J=7.5 Hz, 2H), 3.14 (t, J=6.9 Hz, 2H), 2.35 (s, 3H), 2.32 (s, 3H),2.29 (m, 2H), 2.18 (s, 3H), 1.64–1.94 (m, 4H), 1.07 (t, J=7.5 Hz, 3H),1.06 (t, J=7.2 Hz, 3H).

EXAMPLE 2(39)8-cyclobutylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.36 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.7 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.7, 2.7 Hz, 1H), 6.50 (brd, J=8.4 Hz, 1H), 4.46 (m, 1H),3.81 (s, 3H), 3.12 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.43 (m,2H), 2.30 (s, 3H), 2.23–2.08 (m, 4H), 2.16 (s, 3H), 1.90–1.70 (m, 2H).

EXAMPLE 2(40)8-(N-ethyl-N-cyclobutylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.38 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.12 (d, J=8.7 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=8.7, 2.7 Hz, 1H), 4.74 (m, 1H), 3.99 (m, 2H), 3.83 (s, 3H),3.48 (t, J=7.5 Hz, 2H), 2.98 (t, J=7.5 Hz, 2H), 2.20–2.10 (m, 6H), 2.30(s, 3H), 2.17 (s, 3H), 1.90–1.70 (m, 2H), 1.16 (t, J=7.2 Hz, 3H).

EXAMPLE 2(41)8-(propan-1,3-diol-2-yl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.1, 2.7 Hz, 1H), 6.73 (d, J=10.2 Hz, 1H), 4.12 (m, 1H),3.98–3.83 (m, 4H), 3.82 (s, 3H), 3.05 (t, J=7.2 Hz, 2H), 2.87 (t, J=8.1Hz, 2H), 2.30 (s, 3H), 2.16 (s, 3H), 2.11 (m, 2H).

EXAMPLE 2(42)8-(3-pentylamino)-2-(2-furyl)-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (n-hexane:ethyl acetate=4:1);

NMR (300 MHz, CDCl₃): δ 7.47 (m, 1H), 7.21 (d, J=8.1 Hz, 1H), 6.87 (d,J=2.7 Hz, 1H), 6.81 (dd, J=8.1, 2.7 Hz, 1H), 6.38–6.30 (m, 2H), 6.05 (m,1H), 3.84 (s, 3H), 3.82 (m, 1H), 3.11 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.8Hz, 2H), 2.15 (m, 2H), 2.10 (s, 3H), 1.70 (m, 4H), 1.04 (t, J=7.2 Hz,3H), 1.01 (t, J=7.2 Hz, 3H).

EXAMPLE 2(43)8-(3-pentylamino)-2-phenyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.41 (n-hexane:ethyl acetate=4:1);

NMR (300 MHz, CDCl₃): δ 7.59–7.54 (m, 2H), 7.45–7.19 (m, 5H), 6.88–6.82(m, 2H), 4.04 (m, 1H), 3.85 (s, 3H), 3.55 (t, J=7.8 Hz, 2H), 3.17 (t,J=7.8 Hz, 2H), 2.32 (m, 2H), 2.05 (s, 3H), 1.97–1.55 (m, 4H), 1.10 (t,J=6.9 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H).

EXAMPLE 2(44)8-(2-dimethylaminoethyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (methylene chloride:methanol=19:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.4, 2.7 Hz, 1H), 6.71 (t, J=5.7 Hz, 1H), 3.82 (s, 3H), 3.75(dt, J=5.7, 6.3 Hz, 2H), 3.19 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H),2.63 (t, J=6.3 Hz, 2H), 2.33 (s, 6H), 2.31 (s, 3H), 2.17 (s, 3H), 2.12(m, 2H).

EXAMPLE 2(45)8-(N-methyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine dihydrochloride

TLC: Rf 0.46 (methylene chloride:methanol=9:1);

NMR (300 MHz, pyridine-d₅ 0.5 ml+CDCl₃ 0.1 ml): δ 7.42 (d, J=8.4 Hz,1H), 7.04 (d, J=2.7 Hz, 1H), 6.96 (dd, J=8.4, 2.7 Hz, 1H), 4.21 (t,J=7.5 Hz, 2H), 3.85 (t, J=7.5 Hz, 2H), 3.75 (s, 3H), 3.14 (s, 3H), 3.00(s, 6H), 2.90 (t, J=7.5 Hz, 2H), 2.80 (t, J=7.5 HZ, 2H), 2.41 (s, 3H),2.36 (s, 3H), 1.90 (m, 2H).

EXAMPLE 2(46)8-(N-ethyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (methylene chloride:methanol=9:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.4, 2.7 Hz, 1H), 3.82 (s, 3H), 3.80 (t, J=7.2 Hz, 2H), 3.64(q, J=7.2 Hz, 2H), 2.99 (t, J=7.5 Hz, 2H), 2.90 (t, J=7.5 Hz, 2H), 2.56(t, J=7.2 Hz, 2H), 2.31 (s, 3H), 2.25 (s, 6H), 2.17 (s, 3H), 2.12 (m,2H), 1.17 (t, J=7.2 Hz, 3H).

EXAMPLE 2(47)8-(4-heptylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.50 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.27 (brd, J=9.6 Hz, 1H), 7.11 (d, J=8.4 Hz,1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=8.4, 2.7 Hz, 1H), 4.12 (m, 1H),3.82 (s, 3H), 3.49 (t, J=7.5 Hz, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.32–2.20(m, 2H), 2.28 (s, 3H), 2.20 (s, 3H), 1.82–1.60 (m, 4H), 1.60–1.36 (m,4H), 0.99 (t, J=7.2 Hz, 3H), 0.98 (t, J=7.2 Hz, 3H).

EXAMPLE 2(48)8-(2-butylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.36 (brd, J=9.9 Hz, 1H), 7.12 and 7.11 (d,J=8.4 Hz, two conformers, 1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=8.4,2.7 Hz, 1H), 4.18 (m, 1H), 3.83 (s, 3H), 3.48 (t, J=7.5 Hz, 2H), 3.16(t, J=7.5 Hz, 2H), 2.40–2.20 (m, 2H), 2.28 (s, 3H), 2.19 and 2.18 (s,two conformers, 3H), 1.80 (m, 2H), 1.48 and 1.47 (d, J=6.6 Hz, twoconformers, 3H), 1.09 and 1.08 (t, J=7.2 Hz, two conformers, 3H).

EXAMPLE 2(49)8-(N-propyl-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.13 (m, 1H), 6.88 (brs, 1H), 6.82 (m, 1H), 3.88(m, 2H), 3.83 (brs, 3H), 3.77 (brs, 2H), 3.37 (m, 2H), 3.06 (m, 2H),2.29 (s, 3H), 2.24 (m, 2H), 2.19 (s, 3H), 1.73 (m, 2H), 1.12 (m, 1H),0.96 (m, 3H), 0.62 (m, 2H), 0.26 (brs, 2H).

EXAMPLE 2(50)8-(3-pentylamino)-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, DMSO-d₆): 69.25 (m, 1H), 8.31 (s, 1H), 7.23 (d, J=8.1 Hz,1H), 6.95 (d, J=2.4 Hz, 1H), 6.86 (dd, J=2.4, 8.1 Hz, 1H), 3.99 (m, 1H),3.78 (s, 3H), 3.15 (m, 2H), 3.02 (t, J=7.8 Hz, 2H), 2.20 (s, 3H), 2.18(m, 2H), 1.60–1.88 (m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(51)8-[(2R)-1-methoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.21 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.63 (brd, J=8.4 Hz, 1H), 7.09 (d, J=8.7 Hz,1H), 6.87 (d, J=2.7 Hz, 1H), 6.79 (dd, J=8.7, 2.7 Hz, 1H), 4.19 (m, 1H),3.81 (s, 3H), 3.65–3.53 (m, 2H), 3.45 (t, J=8.1 Hz, 2H), 3.43 and 3.41(s, two conformers, 3H), 3.26–3.01 (m, 2H), 2.30–2.20 (m, 2H), 2.28 (s,3H), 2.18 (s, 3H), 1.96–1.58 (m, 2H), 1.08 and 1.07 (t, J=7.5 Hz, twoconformers, 3H).

EXAMPLE 2(52)8-[(2S)-1-methoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.21 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.59 (brd, J=10.2 Hz, 1H), 7.11 (d, J=8.4 Hz,1H), 6.88 (d, J=2.4 Hz, 1H), 6.81 (dd, J=8.4, 2.7 Hz, 1H), 4.19 (m, 1H),3.83 (s, 3H), 3.66–3.53 (m, 2H), 3.48 (t, J=8.1 Hz, 2H), 3.44 and 3.42(s, two conformers, 3H), 3.26–3.02 (m, 2H), 2.30–2.20 (m, 2H), 2.29 (s,3H), 2.20 (s, 3H), 1.98–1.69 (m, 2H), 1.09 and 1.08 (t, J=7.5 Hz, twoconformers, 3H).

EXAMPLE 2(53)8-cyclopentylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.7 Hz, 1H), 6.84 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.7, 2.7 Hz, 1H), 6.34 (brd, J=9.0 Hz, 1H), 4.38 (m, 1H),3.82 (s, 3H), 3.15 (t, J=7.2 Hz, 2H), 2.89 (t, J=7.8 Hz, 2H), 2.30 (s,3H), 2.17 (s, 3H), 2.18–2.00 (m, 4H), 1.95–1.65 (m, 6H).

EXAMPLE 2(54)8-(3-pentylamino)-2-methyl-3-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.50 (ddd, J=6.6, 8.4, 8.4 Hz, 1H), 6.86–6.99(m, 2H), 6.23 (d, J=10.8 Hz, 1H), 3.80 (m, 1H), 3.09 (t, J=7.2 Hz, 2H),2.92 (t, J=8.1 Hz, 2H), 2.39 (d, J=1.5 Hz, 3H), 2.15 (m, 2H), 1.53–1.81(m, 4H), 1.01 (t, J=7.2 Hz, 6H).

EXAMPLE 2(55)8-(3-pentylamino)-2-trifluoromethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.33 (br d, J=10.2 Hz, 1H), 7.13 (d, J=8.7 Hz,1H), 6.89 (d, J=2.4 Hz, 1H), 6.81 (dd, J=2.4, 8.7 Hz, 1H), 4.04 (m, 1H),3.83 (s, 3H), 3.56 (m, 2H), 3.20 (m, 2H), 2.33 (m, 2H), 2.19 (s, 3H),1.70–2.22 (m, 4H), 1.08 (m, 6H).

EXAMPLE 2(56)8-(N-ethyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.20 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=8.4, 2.7 Hz, 1H), 4.34–4.17 (m, 2H), 3.91 (q, J=7.2 Hz, 2H),3.83 (s, 3H), 3.68 (t, J=5.1 Hz, 2H), 3.47 (t, J=7.8 Hz, 2H), 3.32 (s,3H), 3.06 (t, J=7.2 Hz, 2H), 2.28 (s, 3H), 2.30–2.20 (m, 2H), 2.18 (s,3H), 1.38 (t, J=7.2 Hz, 3H).

EXAMPLE 2(57)8-cyclohexylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.84 (d, J=2.7 Hz, 1H),6.77 (dd, J=8.1, 2.7 Hz, 1H), 6.34 (brd, J=9.6 Hz, 1H), 3.81 (s, 3H),3.80 (m, 1H), 3.10 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.30 (s,3H), 2.17 (s, 3H), 2.18–2.00 (m, 4H), 1.90–1.80 (m, 2H), 1.75–1.60 (m,1H), 1.50–1.20 (m, 5H).

EXAMPLE 2(58)8-(N-propyl-N-(3-pentyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=8.1, 2.7 Hz, 1H), 4.20 (m, 1H), 3.83 (s, 3H), 3.60 (m, 2H),3.38 (t, J=7.5 Hz, 2H), 2.97 (t, J=7.5 Hz, 2H), 2.30–2.15 (m, 2H), 2.27(s, 3H), 2.20 (s, 3H), 2.00–1.70 (m, 4H), 1.42 (m, 2H), 0.98 (t, J=7.5Hz, 6H), 0.90 (t, J=7.5 Hz, 3H).

EXAMPLE 2(59)8-(3-pentylamino)-2-methyl-3-(4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.60 (d, J=9.0 Hz, 2H), 6.99 (d, J=9.0 Hz, 2H),6.10 (br d, J=10.5 Hz, 1H), 3.84 (s, 3H), 3.81 (m, 1H), 3.08 (t, J=7.2Hz, 2H), 2.94 (t, J=7.8 Hz, 2H), 2.53 (s, 3H), 2.15 (m, 2H), 1.53–1.82(m, 4H), 1.00 (t, J=7.2 Hz, 6H).

EXAMPLE 2(60)8-(3-pentylamino)-2-isopropyl-3-(4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.48 (d, J=8.7 Hz, 2H), 6.97 (d, J=8.7 Hz, 2H),6.29 (br d, J=10.5 Hz, 1H), 3.84 (s, 3H), 3.80 (m, 1H), 3.32 (sept,J=6.9 Hz, 1H), 3.07 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.5 Hz, 2H), 2.13 (m,2H), 1.63–1.83 (m, 4H), 1.33 (d, J=6.9 Hz, 6H), 1.01 (t, J=7.5 HZ, 6H).

EXAMPLE 2(61)8-t-butylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.35 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (brd, J=8.7 Hz, 1H), 6.97 (brs, 1H), 6.85(d, J=2.7 Hz, 1H), 6.78 (dd, J=8.7, 2.7 Hz, 1H), 3.81 (s, 3H), 3.15 (t,J=7.2 Hz, 2H), 2.91 (t, J=7.5 Hz, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 2.11(m, 2H), 1.57 (s, 9H).

EXAMPLE 2(62) 8-(3-pentylamino)-3-(2, 4,6-trimethylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.58 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.91 (s, 1H), 7.39 (brd, J=10.2 Hz, 1H), 6.99(s, 2H), 4.03 (m, 1H), 3.52 (t, J=7.8 Hz, 2H), 3.17 (t, J=7.2 Hz, 2H),2.32 (s, 3H), 2.31 (m, 2H), 2.13 (s, 6H), 1.67–1.96 (m, 4H), 1.07 (t,J=7.5 Hz, 6H).

EXAMPLE 2(63)8-(1−cyclobutylethyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.28 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, pyridine-d₅ 0.5 ml+CDCl₃ 0.1 ml): δ 7.46 (d, J=8.1 Hz,1H), 7.06 (d, J=2.7 Hz, 1H), 6.97 (dd, J=8.1, 2.7 Hz, 1H), 6.80 (d,J=10.2 Hz, 1H), 3.96 (m, 1H), 3.74 (s, 3H), 2.97 (ddd, J=14.1, 7.2, 7.2Hz, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.50–2.36 (m, 1H), 2.47 (s, 3H), 2.39(s, 3H), 2.05–1.65 (m, 8H), 1.15 (d, J=6.3 Hz, 3H).

EXAMPLE 2(64)8-(3-pentylamino)-2-methyl-3-(2,3-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.37 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.08 (d, J=8.1 Hz, 1H), 6.78 (d, J=8.1 Hz, 1H),6.21 (d, J=10.8 Hz, 1H), 3.84 (s, 3H), 3.81 (m, 1H), 3.08 (t, J=6.6 Hz,2H), 2.88 (t, J=8.1 Hz, 2H), 2.29 (s, 3H), 2.21 (s, 3H), 2.13 (m, 2H),2.10 (s, 3H), 1.56–1.82 (m, 4H), 1.03 (t, J=7.5 Hz, 3H), 1.01 (t, J=6.9Hz, 3H).

EXAMPLE 2(65)8-(3-pentylamino)-2-methyl-3-(2,5-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.43 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 6.99 (s, 1H), 6.76 (s, 1H), 6.20 (d, J=10.5 Hz,1H), 3.84 (s, 3H), 3.82 (m, 1H), 3.08 (t, J=6.9 Hz, 2H), 2.89 (t, J=7.2Hz, 2H), 2.31 (s, 3H), 2.19 (s, 3H), 2.17 (s, 3H), 2.14 (m, 2H),1.54–1.80 (m, 4H), 1.01 (m, 6H).

EXAMPLE 2(66) 8-(N-(2, 2,2-trifluoroethyl)-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.62 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.1 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.80 (dd, J=8.1, 2.7 Hz, 1H), 4.64 (q, J=9.6 Hz, 2H), 3.82 (s, 3H), 3.41(d, J=6.6 Hz, 2H), 2.98 (t, J=6.9 Hz, 2H), 2.94 (t, J=7.5 Hz, 2H), 2.34(s, 3H), 2.21–2.09 (m, 2H), 2.18 (s, 3H), 1.03 (m, 1H), 0.57 (m, 2H),0.21 (m, 2H).

EXAMPLE 2(67)8-(2,2,2-trifluoroethyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.22 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.1, 2.7 Hz, 1H), 6.75 (brt, J=7.8 Hz, 1H), 4.22 (dq, J=7.8,7.8 Hz, 2H), 3.82 (s, 3H), 3.12 (t, J=7.5 Hz, 2H), 2.92 (t, J=7.8 Hz,2H), 2.31 (s, 3H), 2.23–2.09 (m, 2H), 2.17 (s, 3H).

EXAMPLE 2(68)8-[(2R)-1-methoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.25 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, pyridine-d₅ 0.5 ml+CDCl₃ 0.1 ml): δ 7.39 (d, J=8.1 Hz,1H), 7.37 (brd, J=9.3 Hz, 1H), 7.03 (d, J=2.7 Hz, 1H), 6.95 (dd, J=8.1,2.7 Hz, 1H), 5.45 (d, J=9.9 Hz, 1H), 5.35 (d, J=9.9 Hz, 1H), 4.98 (brs,2H), 3.74 (s, 3H), 3.63–3.48 (m, 3H), 3.26 (s, 3H), 2.41 (s, 3H), 2.34(s, 3H), 1.82–1.60 (m, 2H), 0.97 (t, J=7.5 Hz, 3H).

EXAMPLE 2(69)8-[(2R)-1-methoxybutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-2,3-dihydro-furo[3,2-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, pyridine-d₅ 0.5 ml+CDCl₃ 0.1 ml): δ 7.40 (d, J=8.4 Hz,1H), 7.03 (brs, 1H), 6.95 (dd, J=8.4, 2.4 Hz, 1H), 6.80 (brd, J=9.3 Hz,1H), 4.47 (m, 1H), 4.47 (t, J=8.4 Hz, 2H), 3.74 (s, 3H), 3.56 (d, J=4.8Hz, 2H), 3.28 (s, 3H), 3.12 (t, J=8.4 Hz, 2H), 2.43 (s, 3H), 2.35 (s,3H), 1.87–1.46 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

EXAMPLE 2(70)8-(3-pentylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.33 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.90 (s, 1H), 7.39 (br d, J=10.2 Hz, 1H), 6.72(s, 2H), 4.02 (m, 1H), 3.81 (s, 3H), 3.53 (t, J=7.8 Hz, 2H), 3.17 (t,J=6.9 Hz, 2H), 2.32 (m, 2H), 2.14 (s, 6H), 1.66–1.96 (m, 4H), 1.08 (t,J=7.2 Hz, 6H).

EXAMPLE 2(71)8-(3-pentylamino)-3-(4,6-dimethyl-2-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.33 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.99 (s, 1H), 7.37 (br d, J=10.8 Hz, 1H), 6.75(s, 1H), 6.70 (s, 1H), 4.01 (m, 1H), 3.85 (s, 3H), 3.57 (t, J=7.8 Hz,2H), 3.16 (t, J=7.2 Hz, 2H), 2.36 (s, 3H), 2.31 (m, 2H), 2.23 (s, 3H),1.63–1.92 (m, 4H), 1.06 (t, J=7.2 Hz, 6H).

EXAMPLE 2(72)8-(3-pentylamino)-2-methyl-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 6.68 (s, 2H), 6.21 (d, J=10.5 Hz, 1H), 3.81 (m,1H), 3.80 (s, 3H), 3.09 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.19(s, 3H), 2.13 (m, 2H), 2.04 (s, 6H), 1.55–1.83 (m, 4H), 1.03 (t, J=7.5Hz, 6H).

EXAMPLE 2(73)8-(3-pentylamino)-2-methyl-3-(4,6-dimethyl-2-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 6.75 (m, 1H), 6.62 (s, 1H), 6.21 (d, J=10.5 Hz,1H), 3.80 (m, 1H), 3.71 (s, 3H), 3.06 (m, 2H), 2.87 (m, 2H), 2.34 (s,3H), 2.24 (s, 3H), 2.12 (m, 2H), 2.09 (s, 3H), 1.53–1.80 (m, 4H), 1.03(t, J=7.2 Hz, 3H), 1.00 (t, J=7.5 Hz, 3H).

EXAMPLE 2(74)8-(3-methylpentan-3-yl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.01 (brs, 1H), 7.12 (d, J=8.1 Hz, 1H), 6.89 (d,J=2.7 Hz, 1H), 6.82 (dd, J=8.1, 2.7 Hz, 1H), 3.83 (s, 3H), 3.52 (t,J=7.8 Hz, 2H), 3.16 (t, J=7.2 Hz, 2H), 2.28 (s, 3H), 2.24 (m, 2H), 2.20(s, 3H), 2.00–1.85 (m, 4H), 1.55 (s, 3H), 1.03 (t, J=7.5 Hz, 6H).

EXAMPLE 2(75)8-(3-pentylamino)-2-methyl-3-(5-chloro-1,3-dioxaindan-6-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.44 (benzene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): 66.96 (s, 1H), 6.85 (s, 1H), 6.22 (br d, J=10.5Hz, 1H), 5.99 (s, 2H), 3.80 (m, 1H), 3.08 (t, J=7.2 Hz, 2H), 2.91 (t,J=7.8 Hz, 2H), 2.34 (s, 3H), 2.16 (m, 2H), 1.53–1.81 (m, 4H), 1.01 (t,J=7.2 Hz, 6H).

EXAMPLE 2(76)8-(N-ethyl-N-benzylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.26–7.43 (m, 5H), 7.13 (d, J=8.4 Hz, 1H), 6.89(d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz, 1H), 5.21 (s, 2H), 3.87 (q,J=6.9 Hz, 2H), 3.83 (s, 3H), 3.47 (t, J=7.2 Hz, 2H), 3.03 (t, J=7.2 Hz,2H), 2.29 (s, 3H), 2.22 (m, 2H), 2.19 (s, 3H), 1.39 (t, J=6.9 Hz, 3H).

EXAMPLE 2(77)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-trifluoromethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, pyridene-d₅(0.5 ml),CDCl₃(0.1 ml)): δ 7.71 (d, J=8.4 Hz,1H), 7.57 (m, 1H), 7.28 (m, 1H), 6.77 (d, J=10.5 Hz, 1H), 3.74 (m, 1H),2.95 (t, J=7.5 Hz, 2H), 2.85 (t, J=7.8 Hz, 2H), 2.46 (s, 3H), 1.98 (m,2H), 1.64–1.48 (m, 4H), 0.92 (t, J=7.5 Hz, 6H).

EXAMPLE 2(78)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.20 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, pyridene-d₅(0.5 ml),CDCl₃(0.1 ml)): δ 7.59 (d, J=8.4 Hz,1H), 7.24 (d, J=2.4 Hz, 1H), 6.98 (dd, J=8.4, 2.4 Hz, 1H), 6.78 (d,J=10.5 Hz, 1H), 3.74 (m, 1H), 3.69 (s, 3H), 2.94 (t, J=7.2 Hz, 2H), 2.85(t, J=7.8 Hz, 2H), 2.51 (s, 3H), 1.96 (m, 2H), 1.64–1.48 (m, 4H), 0.91(t, J=7.5 Hz, 6H).

EXAMPLE 2(79)8-(N-benzyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.24 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34–7.44 (m, 3H), 7.27–7.34 (m, 2H), 7.13 (d,J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz, 1H),5.11 (s, 2H), 4.14 (t, J=4.8 Hz, 2H), 3.84 (s, 3H), 3.64 (t, J=4.8 Hz,2H), 3.49 (t, J=7.8 Hz, 2H), 3.29 (s, 3H), 3.07 (t, J=7.2 Hz, 2H), 2.31(s, 3H), 2.23 (m, 2H), 2.19 (s, 3H).

EXAMPLE 2(80)8-(1,2,5,6-tetrahydropyridyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=2.7, 8.1 Hz, CDCl₃), 5.97 (m, 1H), 5.83 (m, 1H), 4.21 (m,2H), 3.85 (m, 2H), 3.82 (s, 3H), 3.07 (t, J=7.2 Hz, 2H), 2.89 (t, J=7.5Hz, 2H), 2.41 (m, 2H), 2.32 (s, 3H), 2.16 (s, 3H), 2.11 (m, 2H).

EXAMPLE 2(81)8-(3-pentylamino)-2-methyl-3-(2-methoxy-4,5-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.29 (brd, J=10.2 Hz, 1H), 7.04 (s, 1H), 6.83(s, 1H), 3.95 (m, 1H), 3.90 (s, 3H), 3.56 (t, J=7.8 Hz, 2H), 3.12 (t,J=7.5 Hz, 2H), 2.42 (s, 3H), 2.31 (s, 3H), 2.28 (m, 2H), 2.24 (s, 3H),1.90–1.62 (m, 4H), 1.04 (t, J=7.5 Hz, 6H).

EXAMPLE 2(82)8-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.24 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.23–7.18 (m, 3H), 7.16 (d, J=8.4 Hz, 1H), 7.11(m, 1H), 6.86 (d, J=2.4 Hz, 1H), 6.79 (dd, J=8.4, 2.4 Hz, 1H), 4.86 (s,2H), 4.09 (t, J=5.7 Hz, 2H), 3.82 (s, 3H), 3.08 (t, J=5.7 Hz, 2H), 2.97(t, J=7.2 Hz, 2H), 2.89 (t, J=7.8 Hz, 2H), 2.33 (s, 3H), 2.17 (s, 3H),2.08 (m, 2H).

EXAMPLE 2(83)8-phenylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.35 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.01 (br, 1H), 7.45–7.38 (m, 2H), 7.33–7.17 (m,4H), 6.87 (d, J=2.4 Hz, 1H), 6.80 (dd, J=8.1, 2.4 Hz, 1H), 3.83 (s, 3H),2.89 (t, J=7.8 Hz, 2H), 2.35 (s, 3H), 2.30 (t, J=7.5 Hz, 2H), 2.21 (s,3H), 2.02–1.90 (m, 2H).

EXAMPLE 2(84)8-(2-methylphenyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.37 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.76 (br, 1H), 7.32–7.17 (m, 5H), 6.87 (d, J=2.4Hz, 1H), 6.80 (dd, J=8.4, 2.4 Hz, 1H), 3.83 (s, 3H), 2.85 (t, J=7.5 Hz,2H), 2.36 (s, 6H), 2.22 (s, 3H), 2.13 (t, J=7.5 Hz, 2H), 1.96–1.85 (m,2H).

EXAMPLE 2(85)8-(3-methylphenyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.96 (br, 1H), 7.32–7.26 (m, 1H), 7.19 (d, J=8.4Hz, 1H), 7.12–7.01 (m, 3H), 6.87 (d, J=2.7 Hz, 1H), 6.80 (dd, J=8.4, 2.7Hz, 1H), 3.83 (s, 3H), 2.88 (t, J=7.8 Hz, 2H), 2.40 (s, 3H), 2.35 (s,3H), 2.31 (t, J=6.9 Hz, 2H), 2.21 (s, 3H), 2.02–1.91 (m, 2H).

EXAMPLE 2(86)8-(4-methylphenyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.33 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.93 (br, 1H), 7.23–7.11 (m, 5H), 6.87 (d, J=2.7Hz, 1H), 6.80 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 2.86 (t, J=7.5 Hz,2H), 2.40 (s, 3H), 2.35 (s, 3H), 2.29 (t, J=7.5 Hz, 2H), 2.21 (s, 3H),2.00–1.88 (m, 2H).

EXAMPLE 2(87)8-(N-phenyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.31–7.24 (m, 2H), 7.21 (d, J=8.4 Hz, 1H),6.99–6.87 (m, 4H), 6.81 (dd, J=8.4, 2.7 Hz, 1H), 4.15–4.07 (m, 2H), 3.84(s, 3H), 2.92 (t, J=7.5 Hz, 2H), 2.36 (s, 3H), 2.31 (t, J=7.5 Hz, 2H),2.22 (s, 3H), 2.05–1.94 (m, 2H), 1.82–1.68 (m, 2H), 0.96 (t, J=7.2 Hz,3H).

EXAMPLE 2(88)8-(N-benzyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.63 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.33–7.21 (m, 5H), 7.19 (d, J=8.4 Hz, 1H), 6.87(d, J=2.7 Hz, 1H), 6.80 (dd, J=8.4, 2.7 Hz, 1H), 4.86 (s, 2H), 3.83 (s,3H), 3.42–3.34 (m, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.81 (t, J=7.1 Hz, 2H),2.36 (s, 3H), 2.20 (s, 3H), 2.11–1.98 (m, 2H), 1.67–1.54 (m, 2H), 0.88(t, J=7.5 Hz, 3H).

EXAMPLE 2(89)8-(N,N-diallylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=2.7, 8.4 Hz, 1H), 6.03 (m, 2H), 5.40 (d, J=10.5 Hz, 2H),5.35 (d, J=18 Hz, 2H), 4.49 (d, J=6.0 Hz, 4H), 3.83 (s, 3H), 3,47 (t,J=7.8 Hz, 2H), 3.08 (t, J=7.2 Hz, 2H), 2.28 (s, 3H), 2.23 (m, 2H), 2.18(s, 3H).

EXAMPLE 2(90)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-dimethylaminophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.17 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.1 Hz, 1H), 6.70 (d, J=2.7 Hz, 1H),6.64 (dd, J=8.1, 2.7 Hz, 1H), 6.19 (d, J=10.2 Hz, 1H), 3.80 (m, 1H),3.08 (t, J=7.5 Hz, 2H), 2.95 (s, 6H), 2.89 (t, J=7.5 Hz, 2H), 2.32 (s,3H), 2.18 (s, 3H), 2.18–2.08 (m, 2H), 1.80–1.56 (m, 4H), 1.01 (brs, 6H).

EXAMPLE 2(91)8-(1−phenylpropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.83 (d, J=8.7 Hz, 1H), 7.27–7.48 (m, 5H), 7.12(d, J=8.4 Hz, 1H), 6.88 (m, 1H), 6.81 (dd, J=2.7, 8.4 Hz, 1H), 5.10 (m,1H), 3.82 (s, 3H), 3.41 (m, 2H), 3.16 (m, 1H), 2.83 (m, 1H), 2.32 (s,3H), 2.20 and 2.19 (s, total 3H), 2.12 (m, 4H), 1.12 and 1.01 (t, J=7.2Hz, total 3H).

EXAMPLE 2(92)8-(N-(2-phenylethyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.35 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.23–7.05 (m, 6H), 6.90 (d, J=2.4 Hz, 1H), 6.83(dd, J=8.4, 2.4 Hz, 1H), 4.33 (t, J=6.6 Hz, 2H), 3.84 (s, 3H), 3.71 (t,J=6.9 Hz, 2H), 3.37 (t, J=7.5 Hz, 2H), 2.98 (t, J=7.2 Hz, 2H), 2.77 (t,J=7.5 Hz, 2H), 2.32 (s, 3H), 2.20 (s, 3H), 2.20–2.06 (m, 2H), 1.81–1.68(m, 2H), 0.97 (t, J=7.5 Hz, 3H).

EXAMPLE 2(93)8-(N-(3-phenylpropyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.26–7.05 (m, 6H), 6.86 (d, J=2.7 Hz, 1H), 6.79(dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 3.66–3.53 (m, 4H), 2.88 (t, J=7.5Hz, 2H), 2.87 (t, J=7.5 Hz, 2H), 2.62 (t, J=7.8 Hz, 2H), 2.32 (s, 3H),2.19 (s, 3H), 2.15–2.04 (m, 2H), 1.95–1.83 (m, 2H), 1.61–1.49 (m, 2H),0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 2(94)8-(N-(4-phenylbutyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.25–7.05 (m, 6H), 6.86 (d, J=2.7 Hz, 1H), 6.78(dd, J=8.1, 2.7 Hz, 1H), 3.83 (s, 3H), 3.63 (t, J=6.6 Hz, 2H), 3.57–3.49(m, 2H), 2.90 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.57 (t, J=6.9Hz, 2H), 2.32 (s, 3H), 2.19 (s, 3H), 2.15–2.05 (m, 2H), 1.66–1.49 (m,6H), 0.88 (t, J=7.5 Hz, 3H).

EXAMPLE 2(95)8-(1−phenyl-2-butyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.41 (hexane:ethyl acetate=2:1);

NMR (300 MHz, DMSO-d₆): δ 9.24 (m, 1H), 7.04–7.30 (m, 6H), 6.95 (brs,1H), 6.86 (dd, J=2.7, 8.4 Hz, 1H), 4.20 (brs, 1H), 3.78 (s, 3H),2.87–3.17 (m, 3H), 2.64–2.87 (m, 3H), 2.26 (s, 3H), 1.82–2.18 (m, 5H),1.63–1.82 (m, 2H), 0.93 (br t, J=6.9 Hz, 3H).

EXAMPLE 2(96)8-(1-phenyl-3-pentyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=2:1);

NMR (300 MHz, DMSO-d₆): δ 8.53 (m, 1H), 7.09–7.28 (m, 6H), 6.96 (d,J=3.0 Hz, 1H), 6.85 (dd, J=3.0, 8.4 Hz, 1H), 4.10 (m, 1H), 3.82 (s, 3H),2.89–3.02 (m, 3H), 2.68–2.85 (m, 3H), 2.25 (s, 3H), 2.00–2.22 (m, 7H),1.79 (m, 2H), 0.93 (t, J=7.5 Hz, 3H).

EXAMPLE 2(97)8-(N-(4-methylphenyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.27 (d, J=8.1 Hz, 2H), 7.13–7.22 (m, 3H), 6.90(d, J=2.4 Hz, 1H), 6.84 (dd, J=2.4, 8.7 Hz, 1H), 4.46 (m, 2H), 3.84 (s,3H), 3.35 (m, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 2.22 (s, 3H), 1.77–1.97(m, 6H), 0.98 (t, J=7.5 Hz, 3H).

EXAMPLE 2(98)8-(N-(4-methylphenyl)methyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.11–7.21 (m, 5H), 6.90 (d, J=2.7 Hz, 1H), 6.83(dd, J=2.7, 8.7 Hz, 1H), 5.13 (s, 2H), 3.84 (s, 3H), 3.72 (t, J=7.5 Hz,2H), 3.48 (t, J=8.1 Hz, 2H), 3.01 (t, J=6.9 Hz, 2H), 2.36 (s, 3H), 2.29(s, 3H), 2.22 (m, 2H), 2.19 (s, 3H), 1.77 (m, 2H), 0.94 (t, J=7.5 Hz,3H).

EXAMPLE 2(99)8-(N-(3-methylphenyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.41 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.36 (m, 1H), 7.06–7.24 (m, 4H), 6.91 (d, J=2.4Hz, 1H), 6.84 (dd, J=2.4, 8.1 Hz, 1H), 4.46 (m, 2H), 3.84 (s, 3H), 3.36(m, 2H), 2.42 (s, 3H), 2.32 (s, 3H), 2.23 (s, 3H), 1.77–2.00 (m, 6H),0.99 (t, J=7.2 Hz, 3H).

EXAMPLE 2(100)8-(N-(4-methoxyphenyl)methyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.18 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.4 Hz, 1H),6.90(d, J=8.7 Hz, 2H), 6.90 (d, J=3.0 Hz, 1H), 6.83 (dd, J=3.0, 8.4 Hz,1H), 5.10 (s, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.70 (t, J=7.5 Hz, 2H),3.49 (t, J=8.1 Hz, 2H), 3.01 (t, J=6.9 Hz, 2H), 2.30 (s, 3H), 2.22 (m,2H), 2.19 (s, 3H), 1.75 (m, 2H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 2(101)8-(N-(4-chlorophenyl)methyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): 7.37 (d, J=8.7 Hz, 2H), 7.24 (d, J=8.7 Hz, 2H),7.12 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz,1H), 5.15 (s, 2H), 3.83 (s, 3H), 3.68 (m, 2H), 3.50 (t, J=7.8 Hz, 2H),3.02 (t, J=7.2 Hz, 2H), 2.29 (s, 3H), 2.25 (m, 2H), 2.19 (s, 3H), 1.74(m, 2H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 2(102)8-(N-(2-methylphenyl)-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.27–7.45 (m, 4H), 7.16 (d, J=8.4 Hz, 1H), 6.90(d, J=2.4 Hz, 1H), 6.84 (dd, J=2.4, 8.4 Hz, 1H), 4.53 (m, 1H), 4.37 (m,1H), 3.84 (s, 3H), 3.34 (m, 2H), 2.31 (s, 3H), 2.23 (s, 3H), 2.10 (s,3H), 1.50–2.07 (m, 6H), 0.97 (t, J=7.5 Hz, 3H).

EXAMPLE 2(103)8-((3S)-3-mehoxymethyl-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.56 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.30–7.05 (m, 5H), 6.90–6.75 (m, 2H), 5.48 (m,1H), 5.03 (d, J=15.6 Hz, 1H), 4.72 (dd, J=15.6, 3.9 Hz, 1H), 3.82 (s,3H), 3.33 and 3.32 (s, 3H), 3.87–3.05 (m, 7H), 2.82 (d, J=15.6 Hz, 1H),2.40–2.10 (m, 2H), 2.29 (s, 3H), 2.25 and 2.11 (s, 3H).

EXAMPLE 2(104)8-(3-pentylamino)-2-methyl-3-(2-dimethylamino-4-methylpyridin-5-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinedihydrochloride

TLC: Rf 0.42 (chloroform:methanol=20:1);

NMR (300 MHz, CDCl₃): δ 8.01 (s, 1H), 7.32 (d, J=10.2 Hz, 1H), 6.85 (s,1H), 4.00 (m, 1H), 3.41 (s, 6H), 3.40 (m, 2H), 3.17 (m, 2H), 2.37 (s,3H), 2.33 (m, 2H), 2.32 (s, 3H), 1.65–1.95 (m, 4H), 1.07 (t, J=7.5 Hz,3H), 1.06 (t, J=7.2 Hz, 3H).

EXAMPLE 2(105)8-((2S)-1-methoxy-3-phenyl-2-propyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.77 (m, 1H), 7.25–7.36 (m, 3H), 7.16–7.23 (m,2H), 7.11 (m, 1H), 6.88 (m, 1H), 6.80 (m, 1H), 4.44 (m, 1H), 3.82 (s,3H), 3.53–3.68 (m, 2H), 3.47 and 3.46 (s, 3H), 3.38 (m, 2H), 3.11 (t,J=7.2 Hz, 2H), 3.08 (m, 1H), 2.81 (m, 1H), 2.31 (s, 3H), 2.20 and 2.17(s, 3H), 2.15 (m, 2H).

EXAMPLE 2(106)8-(N-(4-methylthiophenyl)methyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.25 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.4 Hz, 2H),7.13 (d, J=8.1 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 8.1 Hz,1H), 5.13 (s, 2H), 3.84 (s, 3H), 3.70 (m, 2H), 3.50 (t, J=7.8 Hz, 2H),3.01 (t, J=6.9 Hz, 2H), 2.50 (s, 3H), 2.29 (s, 3H), 2.23 (m, 2H), 2.19(s, 3H), 1.75 (m, 2H), 0.93 (t, J=7.5 Hz, 3H).

EXAMPLE 2(107)8-(4-phenylpiperazin-1-yl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinedihydrochloride

TLC: Rf 0.30 (hexane:ethyl acetate=2:1);

NMR (300 MHz, DMSO-d₆): δ 7.30–7.38 (m, 2H), 7.21–7.29 (m, 2H), 7.12 (d,J=8.4 Hz, 1H), 7.00 (brd, J=6.9 Hz, 1H), 6.95 (d, J=2.7 Hz, 1H), 6.86(dd, J=2.7, 8.4 Hz, 1H), 4.22 (brs, 4H), 3.79 (s, 3H), 3.53 (brs, 4H),3.14 (m, 2H), 2.97 (t, J=7.8 Hz, 2H), 2.21 (s, 3H), 2.15 (m, 2H), 2.06(s, 3H).

EXAMPLE 2(108)8-(4-(2-chlorophenyl)piperazin-1-yl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.41 (dd, J=1.5, 7.8 Hz, 1H), 7.28 (m, 1H), 7.16(d, J=8.1 Hz, 1H), 7.15 (d, J=8.7 Hz, 1H), 7.03 (m, 1H), 6.86 (d, J=2.7Hz, 1H), 6.79 (dd, J=2.7, 8.1 Hz, 1H), 3.90 (m, 4H), 3.82 (s, 3H), 3.33(t, J=4.8H, 4H), 3.16 (t, J=7.5 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.33(s, 3H), 2.17 (s, 3H), 2.14 (m, 2H).

EXAMPLE 2(109)8-(N,N-dibutylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.57 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.12 (d, J=7.8 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.82 (dd, J=2.4, 7.8 Hz, 1H), 3.90 (t, J=7.5 Hz, 4H), 3.83 (s, 3H), 3.48(m, 2H), 3.02 (m, 2H), 2.27 (s, 3H), 2.25 (m, 2H), 2.19 (s, 3H), 1.71(m, 4H), 1.38 (m, 4H), 0.97 (t, J=6.9 Hz, 6H).

EXAMPLE 2(110)8-(N-methyl-N-butylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.1 Hz, 1H), 6.88 (d, J=3.0 Hz, 1H),6.81 (dd, J=3.0, 8.1 Hz, 1H), 3.97 (m, 2H), 3.83 (s, 3H), 3.51 (s, 3H),3.45 (t, J=8.1 Hz, 2H), 3.12 (t, J=6.9 Hz, 2H), 2.26 (s, 3H), 2.23 (m,2H), 2.18 (s, 3H), 1.85 (m, 2H), 1.40 (m, 2H), 0.99 (t, J=7.2 Hz, 3H).

EXAMPLE 2(111)8-(N-(4-methylphenyl)methyl-N-butylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10–7.21 (m, 5H), 6.89 (d, J=2.4 Hz, 1H), 6.83(dd, J=2.4, 8.1 Hz, 1H), 5.13 (s, 2H), 3.83 (s, 3H), 3.77 (t, J=7.2 Hz,2H), 3.48 (t, J=7.8 Hz, 2H), 3.01 (t, J=6.9 Hz, 2H), 2.36 (s, 3H), 2.29(s, 3H), 2.21 (m, 2H), 2.19 (s, 3H), 1.73 (m, 2H), 1.34 (m, 2H), 0.93(t, J=7.2 Hz, 3H).

EXAMPLE 2(112)8-(N-(4-methylphenyl)methyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.23 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.25–7.05 (m, 5H), 6.98–6.78 (m, 2H), 5.06 (s,2H), 4.22–4.03 (m, 2H), 3.84 (s, 3H), 3.75–3.58 (m, 2H), 3.58–3.38 (m,2H), 3.30 (s, 3H), 3.20–2.90 (m, 2H), 2.36 (s, 3H), 2.30 (s, 3H), 2.21(m, 2H), 2.19 (s, 3H).

EXAMPLE 2(113)8-(N-cyclopropyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.35 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.25–6.95 (m, 5H), 6.95–6.73 (m, 2H), 5.40–5.15(m, 2H), 3.83 (s, 3H), 3.65–3.30 (m, 2H), 3.30–2.95 (m, 2H), 2.35 (s,3H), 2.31 (s, 3H), 2.30–2.10 (m, 3H), 2.19 (s, 3H), 1.10–0.80 (m, 4H).

EXAMPLE 2(114)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.37 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30–7.00 (m, 5H), 7.00–6.75 (m, 2H), 5.24 (s,2H), 3.84 (s, 3H), 3.80–3.60 (m, 2H), 3.60–3.35 (m, 2H), 3.20–2.90 (m,2H), 2.34 (s, 3H), 2.29 (s, 3H), 2.22 (s, 2H), 2.11 (s, 3H), 1.38–1.05(m, 1H), 0.75–0.50 (m, 2H), 0.35–0.10 (m, 2H).

EXAMPLE 2(115)8-(N,N-dipropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.59 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H),6.79 (dd, J=2.4, 8.4 Hz, 1H), 3.82 (s, 3H), 3.56 (m, 4H), 2.95 (t, J=7.2Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H), 2.13 (m,2H), 1.58 (m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(116)8-(N-(4-methylphenyl)methyl-N-(2-butynyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.1 Hz, 2H), 7.19 (d, J=8.1 Hz, 2H),7.11 (d, J=8.7 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H), 6.82 (dd, J=2.7, 8.7 Hz,1H), 5.27 (d, J=15.0 Hz, 1H), 5.24 (d, J=15.0 Hz, 1H), 4.41 (m, 2H),3.83 (s, 3H), 3.51 (t, J=7.5 Hz, 2H), 3.22 (t, J=6.9 Hz, 2H), 2.37 (s,3H), 2.28 (s, 3H), 2.25 (m, 2H), 2.17 (s, 3H), 1.91 (t, J=2.4 Hz, 3H).

EXAMPLE 2(117)8-(N-propyl-N-(2-butynyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=2.7, 8.1 Hz, 1H), 4.40 (m, 2H), 3.82 (s, 3H), 3.55 (m, 2H),3.11 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.18 (s,3H), 2.13 (m, 2H), 1.81 (t, J=2.4 Hz, 3H), 1.66 (m, 2H), 0.95 (t, J=7.5Hz, 3H).

EXAMPLE 2(118)8-(5-nonylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (brd, J=10.5 Hz, 1H), 7.12 (d, J=8.7 Hz,1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.7 Hz, 1H), 4.10 (m, 1H),3.83 (s, 3H), 3.49 (t, J=8.1 Hz, 2H), 3.12 (t, J=6.6 Hz, 2H), 2.29 (s,3H), 2.27 (m, 2H), 2.20 (s, 3H), 1.61–1.88 (m, 4H), 1.30–1.53 (m, 8H),0.94 (m, 6H).

EXAMPLE 2(119)8-(N-cyclopentyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CD₃OD): δ 7.20–6.98 (m, 5H), 6.93 (d, J=2.4 Hz, 1H), 6.85(dd, J=8.6, 2.4 Hz, 1H), 5.20 (d, J=16.5 Hz, 1H), 5.09 (d, J=16.5 Hz,1H), 5.02–4.70 (m, 1H), 3.81 (s, 3H), 3.17 (t, J=7.2 Hz, 2H), 2.98 (t,J=7.8 Hz, 2H), 2.29 (s, 3H), 2.22 (s, 3H), 1.98 (s, 3H), 2.40–1.60 (m,10H).

EXAMPLE 2(120)8-(N-cyclopropylmethyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.85 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.28–7.16 (m, 5H), 6.87 (d, J=3.0 Hz, 1H), 6.79(dd, J=3.0, 8.4 Hz, 1H), 4.89 (s, 2H), 3.83 (s, 3H), 3.38 (d, J=6.9 Hz,2H), 2.96 (t, J=7.2 Hz, 2H), 2.89 (t, J=7.2 Hz, 2H), 2.47 (s, 3H), 2.36(s, 3H), 2.19 (s, 3H), 2.09 (quint, J=7.2 Hz, 2H), 1.10–0.95 (m, 1H),0.52–0.42 (m, 2H), 0.10–0.05 (m, 2H).

EXAMPLE 2(121)8-(N-(4-fluorophenyl)methyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.87 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.28–7.16 (m, 3H), 7.03–6.95 (m, 2H), 6.87 (d,J=2.4 Hz, 1H), 6.79 (dd, J=2.4, 8.4 Hz, 1H), 4.80 (s, 2H), 3.83 (s, 3H),3.40–3.32 (m, 2H), 2.89 (t, J=7.5 Hz, 2H), 2.81 (t, J=7.5 Hz, 2H), 2.36(s, 3H), 2.20 (s, 3H), 2.07 (quint, J=7.5 Hz, 2H), 1.62–1.50 (m, 2H),0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 2(122)8-(N-cyclobutyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.19 (d, J=8.4 Hz, 1H), 7.02 (d, J=7.5 Hz, 2H),6.89 (d, J=7.5 Hz, 2H), 6.87 (d, J=3.0 Hz, 1H), 6.80 (dd, J=8.4, 3.0 Hz,1H), 4.90–4.70 (m, 2H), 4.08 (m, 1H), 3.83 (s, 3H), 2.84 (t, J=7.5 Hz,2H), 2.61 (m, 2H), 2.39 (s, 3H), 2.30 (s, 3H), 2.19 (s, 3H), 2.20–2.06(m, 4H), 1.96 (m, 2H), 1.80–1.60 (m, 2H).

EXAMPLE 2(123)8-(N-ethyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.69 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.19 (d, J=8.1 Hz, 1H), 7.14–7.06 (m, 4H), 6.87(d, J=2.7 Hz, 1H), 6.80 (dd, J=2.7, 8.1 Hz, 1H), 4.81 (s, 2H), 3.87 (s,3H), 3.47 (q, J=6.9 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.81 (brt, J=7.8Hz, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.20 (s, 3H), 2.04 (quint, J=7.8Hz, 2H), 1.18 (t, J=6.9 Hz, 3H).

EXAMPLE 2(124)8-(N-propyl-N-(4-trifluoromethylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.79 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.57 (brd, J=8.1 Hz, 2H), 7.44 (brd, J=8.1 Hz,2H), 7.18 (d, J=8.7 Hz, 1H), 6.87 (d, J=2.4 Hz, 1H), 6.79 (dd, J=2.4,8.7 Hz, 1H), 4.91 (s, 2H), 3.83 (s, 3H), 3.49–3.25 (m, 2H), 2.90 (t,J=7.8 Hz, 2H), 2.87 (t, J=7.8 Hz, 2H), 2.35 (s, 3H), 2.19 (s, 3H),2.18–2.00 (m, 2H), 1.62–1.50 (m, 2H), 0.88 (t, J=7.5 Hz, 3H).

EXAMPLE 2(125)8-(N-propyl-N-(tetrahydrofuran-2-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.78 (dd, J=2.7, 8.1 Hz, 1H), 3.84–4.06 (m, 2H), 3.82 (s, 3H), 3.64–3.80(m, 3H), 3.50–3.64 (m, 2H), 2.99 (t, J=7.2 Hz, 2H), 2.91 (t, J=8.1 Hz,2H), 2.32 (s, 3H), 2.19 (s, 3H), 2.13 (m, 2H), 1.74–2,00 (m, 3H),1.42–1.65 (m, 3H), 0.89 (t, J=7.5 Hz, 3H).

EXAMPLE 2(126)8-(N-butyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=2.7, 8.4 Hz, 1H), 3.92 (t, J=5.7 Hz, 2H), 3.82 (s, 3H), 3.57(m, 2H), 3.50 (t, J=5.7 Hz, 2H), 3.28 (s, 3H), 2.98 (t, J=7.8 Hz, 2H),2.91 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.55(m, 2H), 1.33 (m, 2H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 2(127)8-(N-propyl-N-cyclopropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.1, 2.7 Hz, 1H), 3.85 (m, 2H), 3.82 (s, 3H), 3.19 (t, J=7.5Hz, 2H), 3.07 (m, 1H), 2.92 (t, J=7.5 Hz, 2H), 2.31 (s, 3H), 2.18 (s,3H), 2.12 (m, 2H), 1.62 (m, 2H), 0.89 (t, J=7.2 Hz, 3H), 0.80–0.68 (m,4H).

EXAMPLE 2(128)8-(N-cyclobutylmethyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.78 (dd, J=2.7, 8.4 Hz, 1H), 3.82 (s, 3H), 3.82 (t, J=6.0 Hz, 2H), 3.64(d, J=7.5 Hz, 2H), 3.49 (t, J=6.0 Hz, 2H), 3.28 (s, 3H), 2.96 (t, J=7.2Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.62–2.50 (m, 1H), 2.32 (s, 3H), 2.18(s, 3H), 2.20–2.05 (m, 2H), 2.06–1.58 (m, 6H).

EXAMPLE 2(129)8-(3-ethoxycarbonyl-1,2,5,6-tetrahydropyridyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.27 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.27 (m, 1H), 7.09 (d, J=8.1 Hz, 1H), 6.88 (d,J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.1 Hz, 1H), 4.62 (m, 2H), 4.27 (q,J=6.9 Hz, 2H), 4.20 (t, J=5.7 Hz, 2H), 3.83 (s, 3H), 3.47 (t, J=7.2 Hz,2H), 3.16 (t, J=6.0 Hz, 2H), 2.85 (m, 2H), 2.27 (s, 3H), 2.26 (m, 2H),2.17 (s, 3H), 1.34 (t, J=6.9 HZ, 3H).

EXAMPLE 2(130)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.68 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.21 (d, J=7.8 Hz, 2H), 7.16 (d, J=7.8 Hz, 2H),7.13 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz,1H), 5.41 (brs, 2H), 5.27 (m, 2H), 5.22 (brs, 2H), 3.83 (s, 3H), 3.74(m, 2H), 2.37 (s, 3H), 2.31 (s, 3H), 2.20 (s, 3H), 1.24 (m, 1H), 0.67(m, 2H), 0.24 (m, 2H).

EXAMPLE 2(131)8-(3-(3-methyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (m, 1H), 7.15 (d, J=8.7 Hz, 1H), 6.86 (d,J=2.7 Hz, 1H), 6.79 (dd, J=2.7, 8.7 Hz, 1H), 4.57 (m, 2H), 3.94 (m, 2H),3.82 (s, 3H), 3.09 (t, J=7.5 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.71 (m,2H), 2.42 (s, 3H), 2.32 (s, 3H), 2.17 (s, 3H), 2.14 (m, 2H).

EXAMPLE 2(132)8-(4-heptylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.37 (d, J=8.7 Hz, 1H), 7.07 (d, J=2.4 Hz, 1H),6.97 (dd, J=2.4, 8.7 Hz, 1H), 4.13 (m, 1H), 3.85 (s, 3H), 3.35–3.66 (m,2H), 3.13 (t, J=7.5 Hz, 2H), 2.34 (s, 3H), 2.29 (m, 2H), 1.60–1.84 (m,4H), 1.34–1.60 (m, 4H), 1.00 (t, J=7.2 Hz, 3H), 0.99 (t, J=7.5 Hz, 3H).

EXAMPLE 2(133)8-(N-cyclopropylmethyl-N-(2-butyryl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.73 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.1, 2.7 Hz, 1H), 4.54 (brs, 2H), 3.82 (s, 3H), 3.53 (d,J=6.9 Hz, 2H), 3.13 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.33 (s,3H), 2.17 (s, 3H), 2.17–2.08 (m, 2H), 1.81 (t, J=2.7 Hz, 3H), 1.20–1.16(m, 1H), 0.60–0.52 (m, 2H), 0.36–0.28 (m, 2H).

EXAMPLE 2(134)8-(N-(2-methoxyethyl)-N-(2-butyryl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.13 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.4, 2.7 Hz, 1H), 4.44–4.39 (m, 2H), 3.92 (t, J=6.0 Hz, 2H),3.82 (s, 3H), 3.65 (t, J=6.0 Hz, 2H), 3.34 (s, 3H), 3.13 (t, J=7.2 Hz,2H), 2.91 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.17 (s, 3H), 2.17–2.08 (m,2H), 1.81 (t, J=2.7 Hz, 3H).

EXAMPLE 2(135)8-(2-butyrylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.80 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.4 Hz, 1H),6.78 (dd, J=8.4, 2.4 Hz, 1H), 6.53 (t, J=6.9 Hz, 1H), 4.36–4.30 (m, 2H),3.82 (s, 3H), 3.25 (t, J=7.2 Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.31 (s,3H), 2.18 (s, 3H), 2.20–2.08 (m, 2H), 1.83 (t, J=2.1 Hz, 3H).

EXAMPLE 2(136)8-(4-(4-chlorophenyl)-1,2,5,6-tetrahydropyridyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.10 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.42–7.30 (m, 4H), 7.16 (d, J=8.1 Hz, 1H), 6.86(d, J=2.4 Hz, 1H), 6.79 (dd, J=8.1, 2.4 Hz, 1H), 6.22–6.18 (m, 1H),4.50–4.32 (m, 2H), 4.10–3.90 (m, 2H), 3.82 (s, 3H), 3.10 (t, J=6.9 Hz,2H), 2.91 (t, J=7.5 Hz, 2H), 2.82–2.69 (m, 2H), 2.33 (s, 3H), 2.17 (s,3H), 2.17–2.08 (m, 2H).

EXAMPLE 2(137)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.36 (d, J=8.4 Hz, 1H), 7.18 (d, J=8.1 Hz, 2H),7.15 (d, J=8.1 Hz, 2H), 7.08 (d, J=2.7 Hz, 1H), 6.97 (dd, J=8.4, 2.7 Hz,1H), 5.25 (d, J=15.9 Hz, 1H), 5.21 (d, J=15.9 Hz, 1H), 3.85 (s, 3H),3.70 (m, 2H), 3.36–3.62 (m, 2H), 3.07 (t, J=7.2 Hz, 2H), 2.36 (s, 3H),2.35 (s, 3H), 2.23 (m, 2H), 1.23 (m, 1H), 0.63 (m, 2H), 0.18 (m, 2H).

EXAMPLE 2(138)8-(N-propyl-N-(4-trifluoromethyloxyphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (brd, J=8.7 Hz, 2H), 7.18 (d, J=8.4 Hz,1H), 7.15 (brd, J=8.7 Hz, 2H), 6.87 (d, J=2.7 Hz, 1H), 6.80 (dd, J=8.4,2.7 Hz, 1H), 4.84 (s, 2H), 3.83 (s, 3H), 3.41–3.35 (m, 2H), 2.89 (t,J=7.5 Hz, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H),2.19–2.00 (m, 2H), 1.66–1.54 (m, 2H), 0.88 (t, J=7.5 Hz, 3H).

EXAMPLE 2(139)8-(N-(2-butyryl)-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H),6.88 (dd, J=8.7, 2.4 Hz, 1H), 4.54 (q, J=2.1 Hz, 2H), 3.83 (s, 3H), 3.52(d, J=6.6 Hz, 2H), 3.13 (t, J=7.5 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H), 2.37(s, 3H), 2.13 (quint, J=7.5 Hz, 2H), 1.81 (t, J=2.1 Hz, 3H), 1.16–1.02(m, 1H), 0.60–0.52 (m, 2H), 0.32–0.26 (m, 2H).

EXAMPLE 2(140)8-(N-propyl-N-(3-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.27 (m, 1H), 7.15 (m, 1H), 7.13 (d, J=8.1 Hz,1H), 7.05 (m, 2H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.1 Hz, 1H),5.14 (s, 2H), 3.83 (s, 3H), 3.74 (m, 2H), 3.49 (t, J=7.2 Hz, 2H), 3.02(t, J=6.9 Hz, 2H), 2.36 (s, 3H), 2.29 (s, 3H), 2.22 (m, 2H), 2.20 (s,3H), 1.77 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 2(141)8-(N-propyl-N-(2-methylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.18–7.30 (m, 4H), 7.13 (d, J=8.1 Hz, 1H), 6.90(d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 8.1 Hz, 1H), 5.13 (s, 2H), 3.83 (s,3H), 3.78 (m, 2H), 3.49 (t, J=6.9 Hz, 2H), 3.00 (t, J=6.9 Hz, 2H), 2.28(s, 3H), 2.24 (s, 3H), 2.21 (m, 2H), 2.19 (s, 3H), 1.79 (m, 2H), 0.94(t, J=7.2 Hz, 3H).

EXAMPLE 2(142)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-ethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.95 (dd, J=2.4, 8.7 Hz, 1H), 4.07 (m, 2H), 3.99 (m, 1H), 3.34–3.65 (m,2H), 3.13 (t, J=7.8 Hz, 2H), 2.35 (s, 3H), 2.29 (m, 2H), 1.62–1.93 (m,4H), 1.42 (t, J=6.9 Hz, 3H), 1.06 (t, J=7.5 Hz, 3H), 1.05 (t, J=7.2 Hz,3H).

EXAMPLE 2(143)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-ethoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.52 (brd, J=10.2 Hz, 1H), 7.32 (d, J=8.4 Hz,1H), 7.07 (d, J=2.4 Hz, 1H), 6.95 (dd, J=2.4, 8.4 Hz, 1H), 5.49 (d,J=16.5 Hz, 1H), 5.39 (d, J=16.5 Hz, 1H), 5.28 (brs, 2H), 4.07 (m, 2H),3.40 (m, 1H), 2.40 (s, 3H), 1.68–1.98 (m, 4H), 1.43 (t, J=6.9 Hz, 3H),1.07 (t, J=7.2 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H).

EXAMPLE 2(144)8-(N-methyl-N-hexylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.09 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.82 (dd, J=8.4, 2.4 Hz, 1H), 4.01–3.95 (m, 2H), 3.83 (s, 3H), 3.51 (s,3H), 3.51–3.42 (m, 2H), 3.18–3.06 (m, 2H), 2.26 (s, 3H), 2.26–2.18 (m,2H), 2.18 (s, 3H), 1.96–1.80 (m, 2H), 1.44–1.25 (m, 6H), 0.90 (brt,J=6.6 Hz, 3H).

EXAMPLE 2(145)8-(N-methyl-N-(3-pentyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (m, 1H), 4.55 (m, 1H), 3.83 (s, 3H), 3.46 (t, J=7.8 Hz, 2H), 3.27(s, 3H), 3.10 (t, J=6.9 Hz, 2H), 2.26 (s, 3H), 2.45 (m, 2H), 2.19 (s,3H), 1.76–1.98 (m, 4H), 1.01 (t, J=7.2 Hz, 6H).

EXAMPLE 2(146)8-(N-methyl-N-(4-heptyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=3.0 Hz, 1H),6.82 (dd, J=3.0, 8.4 Hz, 1H), 4.80 (m, 1H), 3.83 (s, 3H), 3.47 (t, J=7.5Hz, 2H), 3.27 (s, 3H), 3.09 (t, J=7.5 Hz, 2H), 2.25 (s, 3H), 2.24 (m,2H), 2.19 (s, 3H), 1.64–1.94 (m, 4H), 1.28–1.58 (m, 4H), 0.97 (t, J=7.2Hz, 6H).

EXAMPLE 2(147)8-(N-cyclopropyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.4 Hz, 1H), 7.11 (d, J=7.8 Hz, 2H),7.09 (d, J=2.4 Hz, 1H), 7.02 (d, J=7.8 Hz, 2H), 6.94 (dd, J=2.4, 8.4 Hz,1H), 5.18–5.30 (m, 4H), 5.15 (s, 2H), 3.85 (s, 3H), 2.67 (m, 1H), 2.41(s, 3H), 2.33 (s, 3H), 0.85–1.00 (m, 4H).

EXAMPLE 2(148)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.58 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃) δ 7.35 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.1 Hz, 2H),7.17 (d, J=8.1 Hz, 2H), 7.08 (d, J=2.7 Hz, 1H), 6.96 (dd, J=2.7, 8.4 Hz,1H), 5.10–5.50 (m, 6H), 3.85 (s, 3H), 3.69 (m, 2H), 2.37 (s, 3H), 2.36(s, 3H), 1.21 (m, 1H), 0.65 (m, 2H), 0.22 (m, 2H).

EXAMPLE 2(149)8-(N-cyclobutyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.17 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.1, 2.7 Hz, 1H), 4.35 (quint, J=7.5 Hz, 1H), 3.82 (s, 3H),3.69–3.10 (m, 2H), 2.94 (t, J=6.9 Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.33(s, 3H), 2.22–2.02 (m, 9H), 1.78–1.58 (m, 2H), 1.39 (sext, J=7.8 Hz,2H), 0.84 (t, J=7.8 Hz, 3H).

EXAMPLE 2(150)8-(N-isobutyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinedihydrochloride

TLC: Rf 0.63 (ethyl acetate:acetic acid:water=3:1:1);

NMR (300 MHz, DMSO-d₆): δ 7.11 (d, J=8.4 Hz, 1H), 6.91 (d, J=2.7 Hz,1H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 4.08–3.98 (m, 2H), 3.78 (s, 3H),3.50–3.42 (m, 2H), 3.42–3.32 (m, 2H), 3.01 (brt, J=6.9 Hz, 2H), 2.87(brt, J=7.8 Hz, 2H), 2.79 (s, 3H), 2.77 (s, 3H), 2.25 (s, 3H), 2.18–2.00(m, 2H), 2.08 (s, 3H), 1.80–1.64 (m, 1H), 0.83 (d, J=6.6 Hz, 6H).

EXAMPLE 2(151)8-(N-propyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.34 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.7 Hz, 1H), 7.28–7.24 (m, 2H), 7.08(d, J=3.0 Hz, 1H), 7.05–6.97 (m, 2H), 6.90 (dd, J=8.7, 3.0 Hz, 1H), 5.09(s, 2H), 4.91 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.33–3.27 (m, 2H),2.40 (s, 3H), 1.63 (sext, J=7.8 Hz, 2H), 0.39 (t, J=7.8 Hz, 3H).

EXAMPLE 2(152)8-(N-propyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.36 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.28–7.20 (m, 2H), 7.07(d, J=2.7 Hz, 1H), 7.02–6.94 (m, 2H), 6.89 (dd, J=8.4, 2.7 Hz, 1H), 4.80(s, 2H), 3.84 (s, 3H), 3.36 (brt, J=7.5 Hz, 2H), 2.90 (t, J=7.5 Hz, 2H),2.82 (t, J=7.5 Hz, 2H), 2.39 (s, 3H), 2.07 (quint, J=7.5 Hz, 2H),1.68–1.48 (m, 2H), 0.87 (t, J=7.5 Hz, 3H).

EXAMPLE 2(153)8-(N-cyclopropylmethyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.67 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=8.4 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H),7.22 (d, J=8.4 Hz, 2H), 7.09 (d, J=2.7 Hz, 1H), 6.97 (dd, J=2.7, 8.4 Hz,1H), 5.48 (d, J=16.5 Hz, 1H), 5.37 (d, J=16.5 Hz, 1H), 5.33 (d, J=15.9Hz, 1H), 5.24 (s, 2H), 5.24 (d, J=15.9 Hz, 1H), 3.85 (s, 3H), 3.69 (m,2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.19 (m, 1H), 0.69 (m, 2H), 0.24 (m,2H).

EXAMPLE 2(154)8-(N,N-dipropylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.69 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.96 (dd, J=2.4, 8.7 Hz, 1H), 5.48 (td, J=1.8, 16.8 Hz, 1H), 5.36 (td,J=1.8, 16.8 Hz, 1H), 5.21 (t, J=1.8 Hz, 2H), 3.85 (m, 4H), 3.85 (s, 3H),2.35 (s, 3H), 1.83 (m, 4H), 1.02 (t, J=7.2 Hz, 6H).

EXAMPLE 2(155)8-(N,N-dibutylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.74 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.96 (dd, J=2.4, 8.4 Hz, 1H), 5.47 (d, J=16.5 Hz, 1H), 5.36 (d, J=16.5Hz, 1H), 5.21 (s, 2H), 3.88 (m, 4H), 3.85 (s, 3H), 2.34 (s, 3H), 1.79(m, 4H), 1.42 (m, 4H), 1.00 (t, J=7.2 Hz, 6H).

EXAMPLE 2(156)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.33–7.26 (m, 3H), 7.06 (d, J=2.7 Hz, 1H),7.01–6.95 (m, 2H), 6.88 (dd, J=8.4, 2.7 Hz, 1H), 4.88 (s, 2H), 3.84 (s,3H), 3.38 (d, J=6.9 Hz, 2H), 2.96 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.2 Hz,2H), 2.39 (s, 3H), 2.10 (quint, J=7.2 Hz, 2H), 1.10–0.98 (m, 1H),0.49–0.42 (m, 2H), 0.08–0.02 (m, 2H).

EXAMPLE 2(157)8-(N-propyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.7 Hz, 1H), 7.19 (d, J=8.1 Hz, 2H),7.13 (d, J=8.1 Hz, 2H), 7.08 (d, J=2.7 Hz, 1H), 6.95 (dd, J=2.7, 8.1 Hz,1H), 5.28 (m, 2H), 5.13 (m, 2H), 5.08 (m, 2H), 3.85 (s, 3H), 3.64 (m,2H), 2.37 (s, 3H), 2.36 (s, 3H), 1.80 (m, 2H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 2(158)8-(3-pentylamino)-2-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinedihydrochloride

TLC: Rf 0.19 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.91 (s, 1H), 8.12 (s, 1H), 3.99 (m, 1H), 3.50(m, 2H), 3.15 (m, 2H), 2.47 (s, 3H), 2.32 (m, 2H), 1.94–1.64 (m, 4H),1.06 (brt, J=6.9 Hz, 6H).

EXAMPLE 2(159)8-(N-butyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.21 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.1 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.96 (dd, J=8.1, 2.4 Hz, 1H), 5.47 and 5.35 (ABd, J=16.5 Hz, 2H), 5.21(brs, 2H), 4.00–3.75 (m) and 3.85 (s) total 7H, 2.34 (s, 3H), 1.90–1.75(m, 4H), 1.42 (sext, J=7.2 Hz, 2H), 1.05–0.98 (m, 6H).

EXAMPLE 2(160)8-(N-butyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.33 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.12 (d, J=8.7 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.82 (dd, J=8.7, 2.4 Hz, 1H), 3.95–3.80 (m) and 3.83 (s) total 7H, 3.48(t, J=7.5 Hz, 2H), 3.02 (t, J=7.5 Hz, 2H), 2.30–2.18 (m) and 2.27 (s)total 5H, 2.19 (s, 3H), 1.80–1.65 (m, 4H), 1.38 (sext, J=7.2 Hz, 2H),0.96 (t, J=7.2 Hz, 6H).

EXAMPLE 2(161)8-(4-heptylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.52 (d, J=10.2 Hz, 1H), 7.34 (d, J=8.7 Hz, 1H),7.08 (d, J=2.4 Hz, 1H), 6.97 (dd, J=2.4, 8.7 Hz, 1H), 5.49 (brd. J=16.8Hz, 1H), 5.39 (d, J=16.8 Hz, 1H), 5.28 (m, 2H), 3.85 (s, 3H), 3.53 (m,1H), 2.39 (s, 3H), 1.75 (m, 4H), 1.47 (m, 4H), 1.00 (t, J=7.2 Hz, 6H).

EXAMPLE 2(162)8-(N-butyl-N-ethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.96 (dd, J=2.4, 8.7 Hz, 1H), 5.46 (m, 1H), 5.35 (m, 1H), 5.23 (t, J=1.5Hz, 2H), 3.80–4.00 (m, 4H), 3.85 (s, 3H), 2.34 (s, 3H), 1.80 (m, 2H),1.46 (t, J=7.2 Hz, 3H), 1.44 (m, 2H), 1.01 (t, J=7.2 Hz, 3H).

EXAMPLE 2(163)8-(N-cyclopropyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.80 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.17–7.09 (m, 2H), 7.07(d, J=2.7 Hz, 1H), 6.96–6.93 (m, 2H), 6.90 (dd, J=8.4, 2.7 Hz, 1H), 5.01(s, 2H), 3.84 (s, 3H), 2.97–2.86 (m, 4H), 2.75 (m, 1H), 2.39 (s, 3H),2.03 (m, 2H), 0.80–0.68 (m, 4H).

EXAMPLE 2(164)8-(N-propyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.85 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.24–7.12 (m, 2H), 7.19 (d, J=8.1 Hz, 1H),7.06–6.97 (m, 2H), 6.87 (d, J=2.7 Hz, 1H), 6.80 (dd, J=8.1, 2.7 Hz, 1H),5.00–4.92 (m, 2H), 3.83 (s, 3H), 3.42–3.36 (m, 2H), 2.86 (t, J=7.5 Hz,2H), 2.75 (t, J=7.5 Hz, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 2.02 (quint,J=7.5 Hz, 2H), 1.68–1.46 (m, 2H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 2(165)8-(N-propyl-N-(3-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.86 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30–7.22 (m, 1H), 7.18 (d, J=8.4 Hz, 1H),7.08–7.01 (m, 2H), 6.98–6.90 (m, 1H), 6.87 (d, J=2.4 Hz, 1H), 6.80 (dd,J=8.4, 2.4 Hz, 1H), 4.85 (s, 2H), 3.83 (s, 3H), 3.42–3.36 (m, 2H), 2.89(t, J=7.5 Hz, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H),2.09 (quint, J=7.5 Hz, 2H), 1.68–1.52 (m, 2H), 0.88 (t, J=7.5 Hz, 3H).

EXAMPLE 2(166)8-dicyclopropylmethylamino-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.39 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=2.4, 8.7 Hz, 1H), 6.48 (brd, J=9.9 Hz, 1H), 5.22 (brs, 2H),4.89 (brs, 2H), 3.83 (s, 3H), 2.87 (m, 1H), 2.37 (s, 3H), 1.15 (m, 2H),0.61 (m, 4H), 0.42 (m, 4H).

EXAMPLE 2(167)8-dicyclopropylmethylamino-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.4 Hz, 1H), 7.04 (d, J=2.4 Hz, 1H),6.87 (dd, J=2.4, 8.4 Hz, 1H), 6.37 (brd, J=9.9 Hz, 1H), 3.82 (s, 3H),3.40 (m, 1H), 3.01 (t, J=6.9 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.35 (s,3H), 2.11 (m, 2H), 1.14 (m, 2H), 0.50–0.66 (m, 4H), 0.35–0.50 (m, 4H).

EXAMPLE 2(168)8-(N-butyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.40–7.30 (m, 1H), 7.08 (s, 1H), 7.00–6.90 (m,1H), 4.00–3.80 (m) and 3.85 (s) total 7H, 3.65–3.30 (m, 2H), 3.10–2.95(m, 2H), 2.40–2.20 (m) and 2.33 (s) total 5H, 1.80–1.65 (m, 4H),1.43–1.30 (m, 2H), 0.97 (t, J=6.6 Hz, 6H).

EXAMPLE 2(169)8-(N-cyclopropylmethyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.4 Hz, 1H), 7.05 (d, J=2.7 Hz, 1H),6.88 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 3.64–3.58 (m, 2H), 3.53 (d,J=6.9 Hz, 2H), 3.01 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.2 Hz, 2H), 2.36 (s,3H), 2.14 (quint, J=7.2 Hz, 2H), 1.65–1.55 (m, 2H), 1.05–0.90 (m, 1H),0.91 (t, J=7.5 Hz, 3H), 0.50–0.40 (m, 2H), 0.15–0.05 (m, 2H).

EXAMPLE 2(170)8-(N-cyclopropylmethyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.89 (dd, J=8.4, 2.7 Hz, 1H), 5.23 (s, 2H), 4.91 (s, 2H), 3.83 (s, 3H),3.65–3.50 (m, 4H), 2.38 (s, 3H), 1.63 (quint, J=7.2 Hz, 2H), 1.10–0.98(m, 1H), 0.94 (t, J=7.2 Hz, 3H), 0.56–0.46 (m, 2H), 0.15 (dd, J=10.8,5.1 Hz, 2H).

EXAMPLE 2(171)8-(N-(2-butynyl)-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.7 Hz, 1H), 7.08 (d, J=1.8 Hz, 1H),6.96 (brd, J=8.7 Hz, 1H), 4.56 (d, J=2.1 Hz, 2H), 4.05–3.80 (m) and 3.85(s) total 5H, 3.65–3.30 (m, 2H), 3.25–3.10 (m, 2H), 2.40–2.20 (m) and2.33 (s) total 5H, 1.95–1.80 (m) and 1.89 (s) total 5H, 1.01 (t, J=7.2Hz, 3H).

EXAMPLE 2(172)8-(N-(2-butynyl)-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.7 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.90 (dd, J=8.7, 2.7 Hz, 1H), 5.32 (s, 2H), 4.91 (s, 2H), 4.45 (q, J=2.1Hz, 2H), 3.84 (s, 3H), 3.55–3.45 (m, 2H), 2.38 (s, 3H), 1.82 (t, J=2.1Hz, 3H), 1.72 (sext, J=7.2 Hz, 2H), 0.98 (t, J=7.2 Hz, 3H).

EXAMPLE 2(173)8-(N-butyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.34 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=7.8 Hz, 1H), 7.08 (d, J=2.1 Hz, 1H),6.97 (brd, J=7.8 Hz, 1H), 4.30–4.18 (m, 2H), 3.90–3.78 (m) and 3.85 (s)total 5H, 3.70–3.30 (m) and 3.64 (m) total 4H, 3.30 (s, 3H), 3.08–2.98(m, 2H), 2.40–2.18 (m) and 2.33 (s) total 5H, 1.80–1.65 (m, 2H),1.43–1.35 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 2(174)8-(N-butyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.39 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.40–7.30 (m, 1H), 7.08 (brs, 1H), 7.05–6.95 (m,1H), 5.60–5.35 (m, 2H), 5.30–5.15 (m, 2H), 4.40–4.20 (m, 2H), 3.90–3.70(m) and 3.85 (s) total 7H, 3.35 (s, 3H), 2.35 (s, 3H), 1.85–1.70 (m,2H), 1.50–1.38 (m, 2H), 0.99 (t, J=6.9 Hz, 3H).

EXAMPLE 2(175)8-(N-propyl-N-(4-trifluoromethyloxyphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.42 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.39–7.33 (m, 2H), 7.31 (d, J=8.4 Hz, 1H),7.21–7.15 (m, 2H), 7.08 (d, J=2.4 Hz, 1H), 6.91 (dd, J=8.4, 2.4 Hz, 1H),5.12 (s, 2H), 4.95 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.36–3.28 (m,2H), 2.40 (s, 3H), 1.70–1.54 (m, 2H), 0.89 (t, J=7.5 Hz, 3H).

EXAMPLE 2(176)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.28 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.33–7.26 (m, 2H), 7.18 (d, J=8.4 Hz, 1H),7.03–6.94 (m, 2H), 6.87 (d, J=2.7 Hz, 1H), 6.80 (dd, J=8.4, 2.7 Hz, 1H),4.88 (s, 2H), 3.83 (s, 3H), 3.38 (d, J=6.9 Hz, 2H), 2.95 (t, J=6.9 Hz,2H), 2.89 (t, J=6.9 Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H), 2.09 (quint,J=6.9 Hz, 2H), 1.01 (m, 1H), 0.58–0.42 (m, 2H), 0.20–0.01 (m, 2H).

EXAMPLE 2(177)8-(3-pentylamino)-2-methyl-3-(3,5-dichloropyridin-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.58 (d, J=2.1 Hz, 1H), 7.81 (d, J=2.1 Hz, 1H),6.24 (brd, J=11.1 Hz, 1H), 3.80 (m, 1H), 3.08 (t, J=7.5 Hz, 2H), 2.93(t, J=7.5 Hz, 2H), 2.41 (s, 3H), 2.15 (quint, J=7.5 Hz, 2H), 1.80–1.52(m, 4H), 1.00 (t, J=7.5 Hz, 6H).

EXAMPLE 2(178)8-(N-butyl-N-ethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.96 (dd, J=2.7, 8.4 Hz, 1H), 3.94 (m, 4H), 3.85 (s, 3H), 3.30–3.62 (m,2H), 3.05 (m, 2H), 2.32 (s, 3H), 2.25 (m, 2H), 1.74 (m, 2H), 1.32–1.48(m, 5H), 0.98 (t, J=7.8 Hz, 3H).

EXAMPLE 2(179)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.65 (d, J=8.4 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H),7.13 (d, J=8.7 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 8.7 Hz,1H), 5.37 (s, 2H), 3.83 (s, 3H), 3.66 (m, 2H), 3.52 (t, J=7.5 Hz, 2H),3.11 (t, J=7.2 Hz, 2H), 2.29 (s, 3H), 2.27 (m, 2H), 2.19 (s, 3H), 1.14(m, 1H), 0.65 (m, 2H), 0.17 (m, 2H).

EXAMPLE 2(180)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.52 (brd, J=10.2 Hz, 1H), 7.35 (d, J=8.7 Hz,1H), 7.08 (d, J=2.7 Hz, 1H), 6.96 (dd, J=2.7, 8.7 Hz, 1H), 5.50 (d,J=16.5 Hz, 1H), 5.39 (d, J=16.5 Hz, 1H), 5.29 (s, 2H), 3.85 (s, 3H),3.39 (m, 1H), 2.40 (s, 3H), 1.68–1.98 (m, 4H), 1.06 (m, 6H).

EXAMPLE 2(181)8-(N-cyclopropylmethylamino-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.28 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.34–7.28 (m, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.08(d, J=2.7 Hz, 1H), 7.05–6.98 (m, 2H), 6.901 (dd, J=8.4, 2.7 Hz, 1H),5.21 (s, 2H), 4.93 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.38 (d, J=6.9Hz, 2H), 2.40 (s, 3H), 1.08–0.94 (m, 1H), 0.56–0.48 (m, 2H), 0.14–0.06(m, 2H).

EXAMPLE 2(182)8-(N-benzyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine dihydrochloride

TLC: Rf 0.60 (ethyl acetate:acetic acid:water=3:1:1);

NMR (300 MHz, CD₃OD): δ 7.45–7.32 (m, 5H), 7.18 (d, J=8.4 Hz, 1H), 6.98(d, J=2.7 Hz, 1H), 6.90 (dd, J=8.4, 2.7 Hz, 1H), 5.20 (s, 2H), 4.40 (m,2H), 3.84 (s, 3H), 3.75 (m, 2H), 3.16 (m, 2H), 3.06 (m, 2H), 2.96 (s,6H), 2.35 (s, 3H), 2.38–2.18 (m, 2H), 2.11 (s, 3H).

EXAMPLE 2(183).8-(N-benzyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine dihydrochloride

TLC: Rf 0.80 (ethyl acetate:acetic acid:water=3:1:1);

NMR (300 MHz, CD₃OD): δ 7.60–7.30 (m, 6H), 7.19 (d, J=2.4 Hz, 1H),7.08–7.02 (m, 1H), 5.13 (s, 2H), 4.96 (s, 2H), 4.94 (s, 2H), 4.40–4.24(m, 2H), 3.87 (s, 3H), 3.76 (m, 1H), 3.56 (m, 1H), 2.99 (s, 3H), 2.98(s, 3H), 2.44 (s, 3H).

EXAMPLE 2(184)8-(N-benzyl-N-(2-dimethylaminoethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinedihydrochloride

TLC: Rf 0.27 (chloroform:methanol=9:1);

NMR (300 MHz, CD₃OD): δ 7.46–7.26 (m, 6H), 7.20 (d, J=2.1 Hz, 1H),7.08–7.02 (m, 1H), 5.11 (brs, 2H), 4.34–4.20 (m, 2H), 3.87 (s, 3H),3.76–3.64 (m, 2H), 3.34–2.86 (m) and 2.96 (s) total 10H, 2.41 (s, 3H),2.26–2.10 (m, 2H).

EXAMPLE 2(185)8-(N-(2-butynyl)-N-ethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H),6.82 (dd, J=2.7, 8.4 Hz, 1H), 4.55 (q, J=2.1 Hz, 2H), 4.08 (m, 2H), 3.83(s, 3H), 3.48 (t, J=7.5 Hz, 2H), 3.22 (t, J=6.9 Hz, 2H), 2.28 (s, 3H),2.24 (m, 2H), 2.17 (s, 3H), 1.90 (t, J=2.1 Hz, 3H), 1.47 (t, J=7.2 Hz,3H).

EXAMPLE 2(186)8-(N-(2-butynyl)-N-ethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.95 (dd, J=2.4, 8.4 Hz, 1H), 5.41 (s, 2H), 5.36 (m, 2H), 4.46 (m, 2H),4.08 (m, 2H), 3.85 (s, 3H), 2.36 (s, 3H), 1.89 (t, J=2.7 Hz, 3H), 1.51(t, J=7.2 Hz, 3H).

EXAMPLE 2(187)8-(N-(2-butynyl)-N-ethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.32 (hexane:ethyl acetate=2:1);

NMR (300 Hz, CDCl₃): δ 7.34 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.96 (dd, J=2.7, 8.4 Hz, 1H), 4.54 (m, 2H), 4.09 (m, 2H), 3.85 (s, 3H),3.35–3.64 (m, 2H), 3.22 (t, J=7.2 Hz, 2H), 2.34 (S, 3H), 2.26 (m, 2H),1.90 (t, J=2.4 Hz, 3H), 1.47 (t, J=7.2 Hz, 3H).

EXAMPLE 2(188)8-(N,N-dipropylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.40 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.30 (d, J=8.4 Hz, 1H), 7.05 (d, J=2.7 Hz, 1H),6.88 (dd, J=2.7, 8.4 Hz, 1H), 3.83 (s, 3H), 3.56 (m, 4H), 2.95 (t, J=7.2Hz, 2H), 2.91 (t, J=8.1 Hz, 2H), 2.36 (s, 3H), 2.13 (m, 2H), 1.58 (m,4H), 0.89 (t, J=7.2 Hz, 6H).

EXAMPLE 2(189)8-(N-(2-butynyl)-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (toluene:acetone=5:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.90 (dd, J=8.4, 2.7 Hz, 1H), 5.35 (s, 2H), 4.91 (s, 2H), 4.56 (m, 2H),3.83 (s, 3H), 3.50 (m, 2H), 2.39 (s, 3H), 1.82 (t, J=2.4 Hz, 3H), 1.15(m, 1H), 0.64–0.56 (m, 2H), 0.38–0.28 (m, 2H).

EXAMPLE 2(190)8-(N-propyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.22 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.60 (brd, J=8.1 Hz, 2H), 7.47 (brd, J=8.1 Hz,2H), 7.17 (d, J=8.7 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H), 6.79 (dd, J=8.7,2.7 Hz, 1H), 4.90 (s, 2H), 3.83 (s, 3H), 3.39 (m, 2H), 2.94–2.82 (m,4H), 2.34 (s, 3H), 2.18 (s, 3H), 2.11 (m, 2H), 1.59 (m, 2H), 0.88 (t,J=7.2 Hz, 3H).

EXAMPLE 2(191)8-(N-cyclopropyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.20 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.19–7.13 (m, 2H), 7.08(d, J=2.7 Hz, 1H), 7.06–7.01 (m, 2H), 6.91 (dd, J=8.4, 2.7 Hz, 1H), 5.20(s, 2H), 5.15 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H), 2.46(s, 3H), 2.41 (s, 3H), 0.95–0.88 (m, 4H).

EXAMPLE 2(192)8-(N-propyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.25 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.7 Hz, 1H), 7.20 (s, 4H), 7.08 (d,J=2.7 Hz, 1H), 6.90 (dd, J=8.7, 2.7 Hz, 1H), 5.10 (s, 2H), 4.90 (s, 2H),4.89 (s, 2H), 3.84 (s, 3H), 3.34 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H),1.70–1.50 (m, 2H), 0.89 (t, J=7.5 Hz, 3H).

EXAMPLE 2(193)8-(N-cyclopropyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.19 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.14–7.04 (m, 3H),7.02–6.94 (m, 2H), 6.92 (dd, J=8.4, 2.4 Hz, 1H), 5.19 (s, 2H), 5.16 (s,2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.55 (m, 1H), 2.41 (s, 3H), 0.90–0.76(m, 4H).

EXAMPLE 2(194)8-(N-propyl-N-(3-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.4 Hz, 1H), 7.26–7.15 (m, 2H), 7.07(d, J=2.4 Hz, 1H), 7.05–6.98 (m, 2H), 6.89 (dd, J=8.4, 2.4 Hz, 1H), 4.94(s, 2H), 3.84 (s, 3H), 3.39 (m, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.77 (t,J=7.5 Hz, 2H), 2.40 (s, 3H), 2.04 (quint, J=7.5 Hz, 2H), 1.63 (m, 2H),0.90 (t, J=7.5 Hz, 3H).

EXAMPLE 2(195)8-(N-propyl-N-(3-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.28–7.16 (m, 2H), 7.08(d, J=2.4 Hz, 1H), 7.07–6.99 (m, 2H), 6.91 (dd, J=8.4, 2.4 Hz, 1H), 5.07(s, 2H), 5.04 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.13 (m, 2H), 2.41(s, 3H), 1.68 (sext, J=7.5 Hz, 2H), 0.93 (t, J=7.5 Hz, 3H).

EXAMPLE 2(196)8-dipropylamino-2-methyl-3-(2,5-dichlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.64 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.41 (d, J=8.7 Hz, 1H), 7.40 (d, J=2.4 Hz, 1H),7.23 (dd, J=8.7, 2.4 Hz, 1H), 3.60–3.52 (m, 4H), 2.96 (t, J=7.8 Hz) and2.93 (t, J=7.8 Hz) total 4H, 2.37 (s, 3H), 2.15 (quint, J=7.8 Hz, 2H),1.65–1.50 (m, 4H), 0.89 (t, J=7.2 Hz, 6H).

EXAMPLE 2(197)8-dipropylamino-2-methyl-3-(2,4-dichlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.51 (d, J=2.4 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H),7.29 (dd, J=8.1, 2.4 Hz, 1H), 3.65–3.50 (m, 4H), 2.96 (t, J=7.2 Hz) and2.92 (t, J=7.2 Hz) total 4H, 2.36 (s, 3H), 2.14 (quint, J=7.2 Hz, 2H),1.63–1.45 (m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(198)8-dipropylamino-2-methyl-3-(4-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.58 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.58 (d, J=7.8 Hz, 2H), 7.24 (d, J=7.8 Hz, 2H),3.60–3.52 (m, 4H), 3.00–2.90 (m, 4H), 2.56 (s, 3H), 2.37 (s, 3H), 2.14(quint, J=7.5 Hz, 2H), 1.64–1.48 (m, 4H), 0.87 (t, J=7.2 Hz, 6H).

EXAMPLE 2(199)8-dipropylamino-2-methyl-3-(3-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.50 (s) and 7.47 (d, J=7.5 Hz) total 2H, 7.32(t, J=7.5 Hz, 1H), 7.06 (t, J=7.5 Hz, 1H), 3.60–3.52 (m, 4H), 2.96 (t,J=7.8 Hz, 4H), 2.57 (s, 3H), 2.41 (s, 3H), 2.15 (quint, J=7.8 Hz, 2H),1.64–1.45 (m, 4H), 0.88 (t, J=7.2 Hz, 6H).

EXAMPLE 2(200)8-dipropylamino-2-methyl-3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.56 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.35–7.20 (m, 4H), 3.62–3.54 (m, 4H), 2.96 (t,J=7.2 Hz) and 2.90 (t, J=7.2 Hz) total 4H, 2.34 (s, 3H), 2.22 (s, 3H),2.13 (quint, J=7.2 Hz, 2H), 1.63–1.50 (m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(201)8-(N-propyl-N-(benz[d]1,3-dioxolan-5-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.31 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.18 (d, J=8.1 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.77–6.83 (m, 2H), 6.67–6.75 (m, 2H), 5.94 (s, 2H), 4.74 (s, 2H), 3.83(s, 3H), 3.37 (m, 2H), 2.89 (t, J=7.8 Hz, 2H), 2.85 (t, J=7.5 Hz, 2H),2.35 (s, 3H), 2.20 (s, 3H), 2.08 (m, 2H), 1.58 (m, 2H), 0.88 (t, J=7.2Hz, 3H).

EXAMPLE 2(202)8-(N-propyl-N-(benz[d]1,3-dioxolan-5-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.36 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H),6.97 (dd, J=8.4, 2.7 Hz, 1H), 6.70–6.82 (m, 3H), 6.00 (s, 2H), 5.07 (s,2H), 3.85 (s, 3H), 3.71 (m, 2H), 3.36–3.64 (m, 2H), 3.03 (t, J=7.4 Hz,2H), 2.35 (s, 3H), 2.24 (m, 2H), 1.74 (m, 2H), 0.93 (t, J=7.5 Hz, 3H).

EXAMPLE 2(203)8-(3-pentylamino)-2-methyl-3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.39 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.30–7.18 (m, 4H), 6.23 (d, J=10.5 Hz, 1H),3.90–3.75 (m, 1H), 3.09 (t, J=7.2 Hz, 2H), 2.90 (t, J=7.2 Hz, 2H), 2.32(s, 3H), 2.22 (s, 3H), 2.14 (quint, J=7.2 Hz, 2H), 1.80–1.58 (m, 4H),1.08–0.96 (m, 6H).

EXAMPLE 2(204)8-(3-pentylamino)-2-methyl-3-(3-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.50 (s, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.31 (t,J=7.8 Hz, 1H), 7.05 (d, J=7.8 Hz, 1H), 6.21 (d, J=10.8 Hz, 1H),3.86–3.74 (m, 1H), 3.08 (t, J=7.2 Hz, 2H), 2.95 (t, J=7.2 Hz, 2H), 2.55(s, 3H), 2.41 (s, 3H), 2.15 (quint, J=7.2 Hz, 2H), 1.82–1.55 (m, 4H),1.01 (t, J=7.5 Hz, 6H).

EXAMPLE 2(205)8-(3-pentylamino)-2-methyl-3-(4-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.47 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.57 (d, J=7.8 Hz, 2H), 7.24 (d, J=7.8 Hz, 2H),6.20 (10.5 Hz, 1H), 3.83–3.75 (m, 1H), 3.08 (t, J=7.2 Hz, 2H), 2.94 (t,J=7.2 Hz, 2H), 2.55 (s, 3H), 2.37 (s, 3H), 2.15 (quint, J=7.2 Hz, 2H),1.80–1.52 (m, 4H), 1.00 (t, J=7.2 Hz, 6H).

EXAMPLE 2(206)8-(3-pentylamino)-2-methyl-3-(2-methylthio-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.10 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.26–7.16 (m, 1H), 6.83 (m, 1H), 6.84–6.76 (m,1H), 3.97 (m, 1H), 3.86 (s, 3H), 3.48 (m, 2H), 3.12 (m, 2H), 2.44 (s,3H), 2.33 (s, 3H), 2.28 (m, 2H), 1.95–1.44 (m, 4H), 1.11–0.99 (m, 6H).

EXAMPLE 2(207)8-(N-propyl-N-(benz[d]1,3-dioxolan-5-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H),6.95 (dd, J=2.7, 8.7 Hz, 1H), 6.78–6.83 (m, 2H), 6.72 (m, 1H), 5.99 (s,2H), 5.28 (m, 2H), 5.16 (s, 2H), 5.04 (m, 2H), 3.85 (s, 3H), 3.60 (m,2H), 2.38 (s, 3H), 1.77 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 2(208)8-(N-benzyl-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.25–7.43 (m, 5H), 7.13 (d, J=7.8 Hz, 1H), 6.90(d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 7.8 Hz, 1H), 5.28 (s, 2H), 3.84 (s,3H), 3.69 (m, 2H), 3.48 (t, J=8.1 Hz, 2H), 3.07 (t, J=7.2 Hz, 2H), 2.30(s, 3H), 2.24 (m, 2H), 2.19 (s, 3H), 1.16 (m, 1H), 0.63 (m, 2H), 0.18(m, 2H).

EXAMPLE 2(209)8-(N-benzyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.56 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.25–7.43 (m, 6H), 7.09 (d, J=2.7 Hz, 1H), 6.96(dd, J=2.7, 8.4 Hz, 1H), 5.27 (m, 2H), 3.85 (s, 3H), 3.68 (m, 2H), 3.48(m, 2H), 3.07 (t, J=6.9 Hz, 2H), 2.35 (s, 3H), 2.23 (m, 2H), 1.16 (m,1H), 0.64 (m, 2H), 0.18 (m, 2H).

EXAMPLE 2(210)8-(N-benzyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.26–7.45 (m, 6H), 7.09 (d, J=2.4 Hz, 1H), 6.96(dd, J=2.4, 8.1 Hz, 1H), 5.36 (m, 2H), 5.28 (m, 2H), 5.23 (s, 2H), 3.85(s, 3H), 3.69 (m, 2H), 2.37 (s, 3H), 1.21 (m, 1H), 0.66 (m, 2H), 0.22(m, 2H).

EXAMPLE 2(211)8-(N-butyl-N-(2-butynyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.4, 2.7 Hz, 1H), 4.40 (brs, 2H), 3.82 (s, 3H), 3.59 (m,2H), 3.11 (t, J=7.2 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.18(s, 3H), 2.13 (m, 2H), 1.81 (t, J=2.1 Hz, 3H), 1.63 (m, 2H), 1.38 (m,2H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLE 2(212)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.44 (hexane:ethyl acetate=3:1);

NMR (300 MHz, DMSO-d₆): δ 7.34–7.24 (m, 2H), 7.20–7.10 (m, 1H),4.03–3.85 (m, 1H), 3.14 (brt, J=8.1 Hz, 2H), 2.95 (brt, J=8.1 Hz, 2H),2.25 (s, 3H), 2.25–2.10 (m) and 2.12 (s) total 5H, 1.85–1.60 (m, 4H),0.95–0.85 (m, 6H).

EXAMPLE 2(213)8-(3-pentylamino)-2-methyl-3-(2,5-dichlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=3:1);

NMR (300 MHz, DMSO-d₆): δ 7.68 (d, J=8.4 Hz, 1H), 7.62–7.55 (m) and 7.59(s) total 2H, 4.03–3.85 (m, 1H), 3.14 (brt, J=7.8 Hz, 2H), 2.96 (brt,J=7.8 Hz, 2H), 2.32 (s, 3H), 2.25–2.10 (m, 2H), 1.85–1.60 (m, 4H), 0.89(t, J=7.5 Hz, 6H).

EXAMPLE 2(214)8-(3-pentylamino)-2-methyl-3-(2,4-dimethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

NMR (300 MHz, DMSO-d₆): δ 7.24 (d, J=8.1 Hz, 1H), 6.71 (d, J=2.4 Hz,1H), 6.66 (dd, J=8.1, 2.4 Hz, 1H), 4.05–3.85 (m, 1H), 3.85 (s, 3H), 3.74(s, H), 3.15 (brt, J=8.1 Hz, 2H), 2.99 (brt, J=8.1 Hz, 2H), 2.33 (s,3H), 2.25–2.10 (m, 2H), 1.85–1.63 (m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(215)8-(3-pentylamino)-2-methyl-3-(2-fluoro-4-methylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=3:1);

NMR (300 MHz, DMSO-d₆): 69.20–9.00 (m, 1H), 7.39 (t, J=7.8 Hz, 1H), 7.22(d, J=11.1 Hz, 1H), 7.17 (d, J=7.8 Hz, 1H), 4.05–3.60 (m, 1H, coveredwith H₂O in DMSO-d₆), 3.14 (brt, J=7.8 Hz, 2H), 2.99 (brt, J=7.8 Hz,2H), 2.40 (s, 3H), 2.37 (s, 3H), 2.18 (quint, J=7.8 Hz, 2H), 1.83–1.60(m, 4H), 0.89 (t, J=7.5 Hz, 6H).

EXAMPLE 2(216)8-(N-butyl-N-(2-butynyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.80 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.88 (dd, J=8.7, 2.4 Hz, 1H), 4.39 (q, J=2.1 Hz, 2H), 3.83 (s, 3H), 3.59(m, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.93 (t, J=7.5 Hz, 2H), 2.36 (s, 3H),2.14 (quint, J=7.5 Hz, 2H), 1.81 (t, J=2.1 Hz, 3H), 1.68–1.54 (m, 2H),1.39 (sext, J=7.5 Hz, 2H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLE 2(217)8-(N-butyl-N-(2-butynyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.78 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.7 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.89 (dd, J=8.7, 2.7 Hz, 1H), 5.33 (s, 2H), 4.91 (s, 2H), 4.44 (q, J=2.4Hz, 2H), 3.83 (s, 3H), 3.54 (m, 2H), 2.38 (s, 3H), 1.82 (t, J=2.4 Hz,3H), 1.74–1.61 (m, 2H), 1.41 (sext, J=7.5 Hz, 2H), 0.96 (t, J=7.5 Hz,3H).

EXAMPLE 2(218)8-(3-methyl-2-butylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.45 (brd, J=10.2 Hz, 1H), 7.11 (dd J=4.2, 8.4Hz, 1H), 6.89 (d, J=2.4 Hz, 1H), 6.82 (dd, J=2.4, 8.4 Hz, 1H), 4.07 (m,1H), 3.83 (s, 3H), 3.49 (m, 2H), 3.15 (t, J=6.9 Hz, 2H), 2.29 (m, 2H),2.28 (s, 3H), 2.20 and 2.19 (s, total 3H), 1.99 (m, 1H), 1.42 and 1.41(d, J=6.6 Hz, total 3H), 1.05–1.14 (m, 6H).

EXAMPLE 2(219)8-(1−cyclohexylethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.42 (brd, J=10.5 Hz, 1H), 7.11 and 7.10 (d,J=8.1 Hz, total 1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.1 Hz,1H), 4.03 (m, 1H), 3.82 (s, 3H), 3.48 (m, 2H), 3.12 (t, J=7.5 Hz, 2H),2.28 (m, 2H), 2.28 (s, 3H), 2.20 and 2.18 (s, total 3H), 1.52–1.95 (m,6H), 1.41 and 1.40 (d, J=6.6 Hz, total 3H), 1.01–1.37 (m, 5H).

EXAMPLE 2(220)8-(2-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.34 (brd, J=9.6 Hz, 1H), 7.11 and 7.10 (d,J=8.7 Hz, total 1H), 6.89 (d, J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.7 Hz,1H), 4.25 (m, 1H), 3.83 (s, 3H), 3.49 (m, 2H), 3.16 (t, J=6.9 Hz, 2H),2.29 (m, 2H), 2.28 (s, 3H), 2.20 and 2.19 (s, total 3H), 1.70–1.80 (m,2H), 1.44–1.58 (m, 2H), 1.47 and 1.46 (d, J=6.6 Hz, total 3H), 1.01 (m,3H).

EXAMPLE 2(221)8-(2-heptylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.43 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (brd, J=10.2 Hz, 1H), 7.12 and 7.11 (d,J=8.4 Hz, total 1H), 6.89 (d, J=2.7 Hz, 1H), 6.82 (dd, J=2.7, 8.4 Hz,1H), 4.22 (m, 1H), 3.83 (s, 3H), 3.50 (m, 2H), 3.15 (t, J=6.9 Hz, 2H),2.29 (m, 2H), 2.28 (s, 3H), 2.20 and 2.19 (s, total 3H), 1.71–1.81 (m,2H), 1.30–1.55 (m, 9H), 0.92 (m, 3H).

EXAMPLE 2(222)8-(1−methoxy-2-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.30 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.66 (brd, J=8.4 Hz, 1H), 7.11 and 7.10 (d,J=8.7 Hz, total 1H), 6.88 (d, J=2.7 Hz, 1H), 6.80 (dd, J=2.7, 8.7 Hz,1H), 4.46 (m, 1H), 3.82 (s, 3H), 3.64 (dd, J=3.9, 9.9 Hz, 1H), 3.42–3.58(m, 3H), 3.46 and 3.45 (s, total 3H), 3.23 (m, 1H), 3.11 (m, 1H), 2.29(m, 2H), 2.29 (s, 3H), 2.19 and 2.18 (s, total, 3H), 1.49 (d, J=6.6 Hz,3H).

EXAMPLE 2(223)8-(2-octylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.60 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (brd, J=10.2 Hz, 1H), 7.12 and 7.11 (d,J=8.1 Hz, total 1H), 6.89 (d, J=2.7 Hz, 1H), 6.82 (dd, J=2.7, 8.1 Hz,1H), 4.23 (m, 1H), 3.83 (s, 3H), 3.50 (brt, J=7.2 Hz, 2H), 3.15 (t,J=6.6 Hz, 2H), 2.29 (m, 2H), 2.28 (s, 3H), 2.20 and 2.19 (s, total 3H),1.75 (m, 2H), 1.46 and 1.45 (d, J=6.3 Hz, total 3H), 1.26–1.45 (m, 8H),0.90 (m, 3H).

EXAMPLE 2(224) 8-(1, 2, 3,4-tetrahydronaphthalen-1-yl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.16 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.44 (m, 1H), 7.27–7.14 (m, 4H), 6.85 (d, J=2.7Hz, 1H), 6.78 (dd, J=8.1, 2.7 Hz, 1H), 6.69 (brd, J=9.9 Hz, 1H), 5.22(m, 1H), 3.82 (s, 3H), 3.24–3.08 (m, 2H), 3.00–2.76 (m, 4H), 2.26 (s,3H), 2.24–1.82 (m, 6H), 2.20 (s, 3H).

EXAMPLE 2(225) 8-((1S, 2S, 3S, 5R)-2, 6,6-trimethylbicyclo[3.1.1]-3-heptyl)amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.25 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.85 (d, J=2.4 Hz, 1H),6.78 (dd, J=8.1, 2.4 Hz, 1H), 6.35 (brd, J=10.8 Hz, 1H), 4.31 (m, 1H),3.82 (s, 3H), 3.22–3.06 (m, 2H), 2.91 (t, J=8.1 Hz, 2H), 2.62–2.46 (m,2H), 2.31 (s, 3H), 2.19 (s, 3H), 2.19–1.82 (m, 6H), 1.29 (s, 3H), 1.20(d, J=6.0 Hz, 3H), 1.11–1.08 (m, 1H), 1.09 (s, 3H).

EXAMPLE 2(226)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.41 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.38–7.32 (m, 2H), 7.26–7.10 (m, 2H), 4.04–3.90(m, 1H), 3.60–3.30 (m, 2H), 3.13 (t, J=6.6 Hz, 2H), 2.39 (s, 3H), 2.35(s, 3H), 2.28 (quint, J=6.6 Hz, 2H), 1.92–1.40 (m, 4H), 1.06 (t, J=7.2Hz, 6H).

EXAMPLE 2(227)8-(3-pentylamino)-2-methyl-3-(2,5-dimethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.32–7.24 (m, 1H), 7.00–6.90 (m, 2H), 6.85 (d,J=2.4 Hz, 1H), 4.05–3.95 (m, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.56 (t,J=7.8 Hz, 2H), 3.12 (t, J=7.8 Hz, 2H), 2.43 (s, 3H), 2.29 (quint, J=7.8Hz, 2H), 1.90–1.40 (m, 4H), 1.05 (t, J=7.5 Hz, 6H).

EXAMPLE 2(228)8-(3-pentylamino)-2-methyl-3-(2-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.24 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.41 (t, J=8.1 Hz, 1H), 7.34–7.24 (m, 2H),7.10–7.02 (m, 2H), 4.03–3.90 (m, 1H), 3.94 (s, 3H), 3.56 (t, J=7.5 Hz,2H), 3.12 (t, J=7.5 Hz, 2H), 2.43 (s, 3H), 2.36–2.20 (m, 2H), 1.90–1.40(m, 4H), 1.05 (t, J=7.5 Hz, 6H).

EXAMPLE 2(229)8-dicyclopropylmethylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.87 (m, 1H), 7.11 (d, J=8.7 Hz, 1H), 6.89 (d,J=2.7 Hz, 1H), 6.82 (dd, J=2.7, 8.7 Hz, 1H), 5.37 (s, 2H), 5.19 (m, 2H),3.83 (s, 3H), 2.90 (m, 1H), 2.36 (s, 3H), 2.20 (s, 3H), 1.26 (m, 2H),0.66–0.85 (m, 4H), 0.47 (m, 4H).

EXAMPLE 2(230)8-(N-butyl-N-ethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.7 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=2.7, 8.7 Hz, 1H), 5.40 (s, 2H), 5.23 (s, 2H), 3.85–4.00 (m,4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.82 (m, 2H), 1.46 (t,J=6.9 Hz, 3H), 1.44 (m, 2H), 1.02 (t, J=6.9 Hz, 3H).

EXAMPLE 2(231)8-(N-butyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.82 (dd, J=2.4, 8.4 Hz, 1H), 5.40 (s, 2H), 5.21 (s, 2H), 3.87 (m, 4H),3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.82 (m, 4H), 1.42 (m, 2H),1.02 (t, J=7.2 Hz, 3H), 1.00 (t, J=7.2 Hz, 3H).

EXAMPLE 2(232)8-(N,N-dipropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.89 (d, J=3.0 Hz, 1H),6.82 (dd, J=3.0, 8.4 Hz, 1H), 5.39 (brs, 2H), 5.21 (brs, 2H), 3.85 (m,4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.83 (m, 4H), 1.02 (t,J=7.2 Hz, 6H).

EXAMPLE 2(233)8-(N-ethyl-N-(4-hydroxybutyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=1:2);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.87 (d, J=3.0 Hz, 1H),6.79 (dd, J=3.0, 8.4 Hz, 1H), 3.87–4.01 (m, 4H), 3.82 (s, 3H), 3.65 (t,J=6.0 Hz, 2H), 3.38 (t, J=7.5 Hz, 2H), 3.06 (t, J=7.2 Hz, 2H), 2.27 (s,3H), 2.24 (m, 2H), 2.17 (s, 3H), 1.86 (m, 2H), 1.61 (m, 2H), 1.38 (t,J=7.2 Hz, 3H).

EXAMPLE 2(234)8-bis(2-methoxyethyl)amino-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.96 (dd, J=2.4, 8.4 Hz, 1H), 5.40 (m, 1H), 5.33 (m, 1H), 5.25 (m, 2H),4.15 (m, 4H), 3.85 (s, 3H), 3.71 (t, J=5.1 Hz, 4H), 3.35 (s, 6H), 2.35(s, 3H).

EXAMPLE 2(235)8-(3-pentylamino)-2-methyl-3-(2-methoxy-5-isopropylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.36 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.23 (dd, J=8.4, 2.1 Hz, 1H), 7.12 (d, J=2.1 Hz,1H), 6.98 (d, J=8.4 Hz, 1H), 4.00–3.85 (m) and 3.91 (s) total 4H,3.58–3.30 (m, 2H), 3.11 (t, J=6.9 Hz, 2H), 2.92 (m, 1H), 2.43 (s, 3H),2.35–2.20 (m, 2H), 1.90–1.50 (m, 4H), 1.26 (d, J=6.9 Hz, 6H), 1.04 (t,J=7.5 Hz, 6H).

EXAMPLE 2(236)8-(3-pentylamino)-2-methyl-3-(2-methoxy-5-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.20–6.95 (m, 4H), 4.04–3.80 (m) and 3.91 (s)total 4H, 3.52–3.40 (m, 2H), 3.12 (t, J=7.2 Hz, 2H), 2.43 (s, 3H), 2.27(quint, J=7.2 Hz, 2H), 1.90–1.40 (m, 4H), 1.05 (t, J=7.5 Hz, 6H).

EXAMPLE 2(237)8-(N-butyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.44–7.20 (m, 3H), 7.14–6.90 (m, 4H), 5.03 (brs,2H), 3.85 (s, 3H), 3.62 (m, 2H), 3.29 (m, 2H), 2.96 (m, 2H), 2.37 (s,3H), 2.19 (m, 2H), 1.65 (m, 2H), 1.32 (m, 2H), 0.90 (m, 3H).

EXAMPLE 2(238)8-(N-butyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.20 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.40–7.26 (m, 3H), 7.12 (brd, J=7.8 Hz, 2H),7.09 (d, J=2.1 Hz, 1H), 6.99–6.92 (m, 1H), 5.40 (m, 2H), 5.30–5.08 (m,4H), 3.85 (s, 3H), 3.70 (m, 2H), 2.37 (s, 3H), 1.76 (m, 2H), 1.36 (m,2H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLE 2(239)8-(N-butyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.28 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.29 (m, 2H), 7.18–7.04 (m, 3H), 6.89 (d, J=2.1Hz, 1H), 6.85–6.78 (m, 1H), 5.23 (m, 2H), 5.15 (m, 2H), 5.11 (m, 2H),3.83 (s, 3H), 3.58 (m, 2H), 2.33 (s, 3H), 2.20 (s, 3H), 1.71 (m, 2H),1.35 (m, 2H), 0.95–0.84 (m, 3H).

EXAMPLE 2(240)8-(3-pentylamino)-2-methyl-3-(2-methoxy-5-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.33 (dd, J=9.0, 3.0 Hz, 1H), 7.25–7.05 (m) and7.22 (d, J=3.0 Hz) total 2H, 6.98 (d, J=9.0 Hz, 1H), 4.03–3.85 (m) and3.93 (s) total 4H, 3.55–3.40 (m, 2H), 3.13 (t, J=7.2 Hz, 2H), 2.43 (s,3H), 2.28 (quint, J=7.2 Hz, 2H), 1.90–1.40 (m, 4H), 1.05 (t, J=7.5 Hz,6H).

EXAMPLE 2(241)8-(N-ethyl-N-(2-butyryl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.37 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=2.7, 8.4 Hz, 1H), 5.41 (s, 4H), 4.48 (m, 2H), 4.14 (m, 2H),3.83 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 1.90 (t, J=2.4 Hz, 3H), 1.54(t, J=7.2 Hz, 3H).

EXAMPLE 2(242)8-(N-propyl-N-(2-butyryl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.1 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H),6.82 (dd, J=2.7, 8.1 Hz, 1H), 5.41 (m, 2H), 5.39 (m, 2H), 5.42 (m, 2H),3.98 (m, 2H), 3.83 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 1.94 (m, 2H),1.89 (t, J=2.7 Hz, 3H), 1.05 (t, J=7.2 Hz, 3H).

EXAMPLE 2(243)8-(N-propyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.27 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H),7.12 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz,1H), 5.40 (s, 2H), 5.11–5.26 (m, 4H), 3.84 (s, 3H), 3.70 (m, 2H), 2.50(s, 3H), 2.31 (s, 3H), 2.20 (s, 3H), 1.84 (m, 2H), 0.97 (t, J=7.2 Hz,3H).

EXAMPLE 2(244)8-(N-propyl-N-(benz[d]1,3-dioxolan-5-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.13 (d, J=8.1 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H),6.83 (dd, J=2.7, 8.1 Hz, 1H), 6.82 (d, J=7.5 Hz, 1H), 6.78 (d, J=1.5 Hz,1H), 6.73 (dd, J=1.5, 7.5 Hz, 1H), 6.01 (s, 2H), 5.39 (s, 2H), 5.17 (s,2H), 5.11 (m, 2H), 3.84 (s, 3H), 3.69 (m, 2H), 2.32 (s, 3H), 2.21 (s,3H), 1.81 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 2(245)8-(N-benzyl-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34–7.46 (m, 3H), 7.26–7.33 (m, 2H), 7.13 (d,J=8.7 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.84 (dd, J=2.7, 8.7 Hz, 1H),5.42 (s, 2H), 5.33 (m, 2H), 5.24 (s, 2H), 3.84 (s, 3H), 3.73 (m, 2H),2.31 (s, 3H), 2.20 (s, 3H), 1.24 (m, 1H), 0.69 (m, 2H), 0.24 (m, 2H).

EXAMPLE 2(246)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.62 (brd, J=7.8 Hz, 2H), 7.48 (brd, J=7.8 Hz,2H), 7.34 (brd, J=8.1 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H), 6.90–6.88 (m,1H), 5.19 (brs, 2H), 3.85 (s, 3H), 3.54 (m, 2H), 3.36–3.14 (m, 2H),3.14–2.98 (m, 2H), 2.36 (s, 3H), 2.22 (m, 2H), 1.12–0.98 (m, 1H),0.64–0.52 (m, 2H), 0.18–0.08 (m, 2H).

EXAMPLE 2(247)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.65 (brd, J=7.5 Hz, 2H), 7.49 (brd, J=7.5 Hz,2H), 7.33 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H), 6.95 (dd, J=8.4,2.4 Hz, 1H), 5.35–5.18 (m, 6H), 3.85 (s, 3H), 3.54 (d, J=6.6 Hz, 2H),2.36 (s, 3H), 1.11 (m, 1H), 0.72–0.60 (m, 2H), 0.22–0.14 (m, 2H).

EXAMPLE 2(248)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.68 (d, J=7.8 Hz, 2H), 7.49 (d, J=7.8 Hz, 2H),7.12 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.83 (dd, J=8.4, 2.7 Hz,1H), 5.42 (m, 2H), 5.38 (s, 2H), 5.27 (s, 2H), 3.83 (s, 3H), 3.61 (m,2H), 2.30 (s, 3H), 2.19 (s, 3H), 1.15 (m, 1H), 0.74–0.66 (m, 2H),0.26–0.18 (m, 2H).

EXAMPLE 2(249)8-(N-propyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.66 (brd, J=7.8 Hz, 2H), 7.49 (brd, J=7.8 Hz,2H), 7.15 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=8.4,2.7 Hz, 1H), 5.15 (brs, 2H), 5.09 (brs, 2H), 5.01 (brs, 2H), 3.83 (s,3H), 3.37 (m, 2H), 2.33 (s, 3H), 2.18 (s, 3H), 1.74–1.60 (m, 2H), 0.91(t, J=6.9 Hz, 3H).

EXAMPLE 2(250)8-(N-cyclopropyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.16–7.07 (m, 3H),7.02–6.94 (m 2H), 6.92 (dd, J=8.4, 3.0 Hz, 1H), 5.20 (s, 2H), 5.18 (s,2H), 4.94 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H), 2.41 (s, 3H), 0.89–0.79(m, 4H).

EXAMPLE 2(251)8-(N-cyclopropyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.19–7.08 (m, 3H), 7.04–6.96 (m, 2H), 6.88 (d,J=2.7 Hz, 1H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 5.28–5.18 (m, 4H), 5.00 (s,2H), 3.83 (s, 3H), 2.60 (m, 1H), 2.38 (s, 3H), 2.18 (s, 3H), 0.90–0.80(m, 4H).

EXAMPLE 2(252)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.36–7.29 (m, 2H), 7.15–7.05 (m, 3H), 6.90 (d,J=2.7 Hz, 1H), 6.84 (dd, J=8.1, 2.7 Hz, 1H), 5.39 (s, 2H), 5.32–5.20 (m,4H), 3.84 (s, 3H), 3.62 (m, 2H), 2.32 (s, 3H), 2.20 (s, 3H), 1.20–1.08(m, 1H), 0.72–0.62 (m, 2H), 0.28–0.18 (m, 2H).

EXAMPLE 2(253)8-(N-propyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.35 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.97 (dd, J=8.7, 2.4 Hz, 1H), 5.48 (d, J=16.8 Hz, 1H), 5.36 (d, J=16.8Hz, 1H), 5.23 (s, 2H), 4.38–4.22 (m, 2H), 3.85 (s, 3H), 3.78–3.66 (m,4H), 3.34 (s, 3H), 2.35 (s, 3H), 1.81 (sext, J=7.5 Hz, 2H), 1.01 (t,J=7.5 Hz, 3H).

EXAMPLE 2(254)8-(N-propyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.33 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.83 (dd, J=8.4, 2.4 Hz, 1H) 5.41 (s, 2H), 5.22 (s, 2H), 4.30 (m, 2H),3.83 (s, 3H), 3.80–3.60 (m, 4H), 3.34 (s, 3H), 2.30 (s, 3H), 2.19 (s,3H), 1.81 (sext, J=7.5 Hz, 2H), 1.01 (t, J=7.5 Hz, 3H).

EXAMPLE 2(255)8-(3-pentylamino)-2-methyl-3-(2-methyl-4-cyanophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.65 (s, 1H), 7.57 (d. J=7.8 Hz, 1H), 7.34 (d,J=7.8 Hz, 1H), 7.24–7.08 (m, 1H), 4.06–3.88 (m, 1H), 3.41 (brt, J=7.2Hz, 2H), 3.15 (t, J=7.2 Hz, 2H), 2.40–2.20 (m) and 2.30 (s) total 8H,1.90–1.40 (m, 4H), 1.06 (t, J=6.6 Hz, 6H).

EXAMPLE 2(256)8-(N-propyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (brd, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz,1H), 6.99–6.91 (m, 1H), 4.20 (m, 2H), 3.85 (s, 3H), 3.75 (m, 2H), 3.62(m, 2H), 3.52–3.30 (m, 2H), 3.30 (s, 3H), 3.03 (m, 2H), 2.33 (s, 3H),2.24 (m, 2H), 1.72 (m, 2H), 0.96 (t, J=7.5 Hz, 3H).

EXAMPLE 2(257)8-(N-ethyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.40–7.30 (m, 1H), 7.30–7.16 (m, 4H), 7.08 (d,J=2.4 Hz, 1H), 6.99–6.92 (m, 1H), 5.11 (brs, 2H), 3.85 (s, 3H), 3.78 (m,2H), 3.42 (m, 2H), 3.00 (m, 2H), 2.50 (s, 3H), 2.35 (s, 3H), 2.21 (m,2H), 1.34 (m, 3H).

EXAMPLE 2(258)8-(N-ethyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.35 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=8.7 Hz, 1H), 7.28 (brd, J=8.1 Hz,2H), 7.21 (brd, J=8.1 Hz, 2H), 7.09 (d, J=2.7 Hz, 1H), 6.97 (dd, J=8.7,2.7 Hz, 1H), 5.48–5.27 (m, 2H), 5.27–5.06 (m, 4H), 3.85 (s, 3H),3.88–3.78 (m, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.42 (t, J=6.9 Hz, 3H).

EXAMPLE 2(259)8-(N-ethyl-N-(4-methylthiophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.28 (brd, J=8.4 Hz, 2H), 7.22 (brd, J=8.4 Hz,2H), 7.13 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.84 (dd, J=8.4,2.7 Hz, 1H), 5.40 (brs, 2H), 5.22–5.08 (m, 4H), 3.86 (m, 2H), 3.84 (s,3H), 2.50 (s, 3H), 2.31 (s, 3H), 2.20 (s, 3H), 1.43 (t, J=6.6 Hz, 3H).

EXAMPLE 2(260)8-(3-pentylamino)-2-methyl-3-(4-methylthiophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.46 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.52 (d, J=8.4 Hz, 2H), 7.39 (d, J=8.4 Hz, 2H),7.31 (d, J=10.5 Hz, 1H), 4.06–3.90 (m, 1H), 3.60 (t, J=7.8 Hz, 2H), 3.13(t, J=7.8 Hz, 2H), 2.52 (s, 3H), 2.49 (s, 3H), 2.30 (quint, J=7.8 Hz,2H), 1.94–1.64 (m, 4H), 1.05 (t, J=7.2 Hz, 6H).

EXAMPLE 2(261)8-(N-butyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.61 (hexane:ethyl acetate=1:2);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.82 (dd, J=8.4, 2.4 Hz, 1H), 5.40 (s, 2H), 5.22 (s, 2H), 4.29 (m, 2H),3.83 (s, 3H), 3.78 (m, 2H), 3.72 (t, J=5.1 Hz, 2H), 3.34 (s, 3H), 2.30(s, 3H), 2.19 (s, 3H), 1.77 (quintet, J=7.5 Hz, 2H), 1.42 (sixtet, J=7.5Hz, 2H), 1.00 (t, J=7.5 Hz, 3H).

EXAMPLE 2(262)8-(3-pentylamino)-2-methyl-3-(4-dimethylaminophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.57 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.72 (d, J=7.8 Hz, 2H), 7.60–7.40 (m, 2H),6.88–6.75 (m, 1H), 3.98–3.85 (m, 1H), 3.35–3.25 (m, 2H), 3.15–3.05 (m)and 3.13 (s) total 8H, 2.52 (s, 3H), 2.25 (quint, J=7.8 Hz, 2H),1.85–1.60 (m, 4H), 1.03 (t, J=7.5 Hz, 6H).

EXAMPLE 2(263)8-(N-cyclopropylmethyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H),6.81 (dd, J=8.4, 2.4 Hz, 1H), 5.24 (s, 2H), 5.04 (s, 2H), 3.83 (s, 3H),3.69–3.63 (m, 4H), 2.33 (s, 3H), 2.18 (s, 3H), 1.70 (sixt, J=7.5 Hz,2H), 1.07 (m, 1H), 0.96 (t, J=7.5 Hz, 3H), 0.56 (m, 2H), 0.20 (m, 2H).

EXAMPLE 2(264)8-(N-propyl-N-(5-methylfuran-2-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H),6.90 (dd, J=2.7, 8.4 Hz, 1H), 6.02 (d, J=3.0 Hz, 1H), 5.86 (m, 1H), 5.08(s, 2H), 4.91 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.26 (m, 2H), 2.41(s, 3H), 2.23 (s, 3H), 1.66 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 2(265)8-(N-propyl-N-(5-methylfuran-2-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.18 (d, J=8.1 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H),6.81 (d, J=2.4, 8.1 Hz, 1H), 6.01 (d, J=3.0 Hz, 1H), 5.86 (m, 1H), 5.07(s, 2H), 4.91 (s, 2H), 4.88 (s, 2H), 3.83 (s, 3H), 3.25 (m, 2H), 2.37(s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 1.67 (m, 2H), 0.94 (t, J=7.5 Hz,3H).

EXAMPLE 2(266)8-(N-cyclopropylmethyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H),6.80 (dd, J=8.1, 2.4 Hz, 1H), 5.25 (s, 2H), 4.90 (s, 2H), 4.05 (t, J=5.4Hz, 2H), 3.83 (s, 3H), 3.56 (t, J=5.4 Hz, 2H), 3.48 (d, J=6.9 Hz, 2H),3.29 (s, 3H), 2.34 (s, 3H), 2.17 (s, 3H), 1.04 (m, 1H), 0.56 (m, 2H),0.22 (m, 2H).

EXAMPLE 2(267)8-(N-propyl-N-(4-trifluoromethyloxyphenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.36 (brd, J=8.1 Hz, 2H), 7.18 (brd, J=8.1 Hz,2H), 7.17 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H), 6.81 (dd, J=8.4,2.4 Hz, 1H), 5.13 (brs, 2H), 4.97 (brs, 2H), 4.92 (brs, 2H), 3.83 (s,3H), 3.34 (m, 2H), 2.36 (s, 3H), 2.18 (s, 3H), 1.64 (m, 2H), 0.90 (t,J=7.2 Hz, 3H).

EXAMPLE 2(268)8-(N-propyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine hydrochloride

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32–7.22 (m, 2H), 7.17 (brd, J=8.7 Hz, 1H),7.02 (m, 2H), 6.88 (d, J=2.4 Hz, 1H), 6.82 (brd, J=8.7 Hz, 1H), 5.11(brs, 2H), 4.95 (brs, 4H), 3.83 (s, 3H), 3.34 (m, 2H), 2.36 (s, 3H),2.19 (s, 3H), 1.65 (m, 2H), 0.90 (t, J=6.9 Hz, 3H).

EXAMPLE 2(269)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methylthiophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.64 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.40–7.34 (m, 2H), 7.33–7.24 (m, 2H), 3.99 (m,1H), 3.66–3.35 (m, 2H), 3.13 (t, J=7.5 Hz, 2H), 2.52 (s, 3H), 2.35 (s,3H), 2.30 (m, 2H), 1.94–1.64 (m, 4H), 1.10–1.00 (m, 6H).

EXAMPLE 2(270)8-(N-cyclopropylmethyl-N-(2-butynyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H),6.81 (dd, J=8.1, 2.7 Hz, 1H), 5.37 (s, 2H), 5.05 (s, 2H), 4.58 (s, 2H),3.83 (s, 3H), 3.62 (m, 2H), 2.35 (s, 3H), 2.17 (s, 3H), 1.84 (s, 3H),1.20 (m, 1H), 0.63 (m, 2H), 0.36 (m, 2H).

EXAMPLE 2(271)8-(N-(2-methoxyethyl)-N-(2-butynyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.13 (d, J=8.1 Hz, 1H), 6.87 (d, J=2.4 Hz, 1H),6.81 (dd, J=8.1, 2.4 Hz, 1H), 5.39 (s, 2H), 5.06 (s, 2H), 4.42 (s, 2H),4.06 (m, 2H), 3.83 (s, 3H), 3.81 (m, 2H), 3.37 (s, 3H), 2.33 (s, 3H),2.17 (s, 3H), 1.85 (s, 3H).

EXAMPLE 2(272)8-(N-(2-methoxyethyl)-N-(2-butynyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.39 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 5.37 (s, 2H), 4.92 (s, 2H), 4.36 (m, 2H),3.95 (t, J=5.4 Hz, 2H), 3.83 (s, 3H), 3.76 (t, J=5.4 Hz, 2H), 3.36 (s,3H), 2.37 (s, 3H), 1.83 (s, 3H).

EXAMPLE 2(273)8-(N-(2-methoxyethyl)-N-(2-butynyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.93 (dd, J=8.4, 2.7 Hz, 1H), 4.53 (m, 2H), 4.18 (m, 2H), 3.84 (s, 3H),3.81 (t, J=4.8 Hz, 2H), 3.36 (s, 3H), 3.30 (m, 2H), 3.20 (t, J=7.2 Hz,2H), 2.34 (s, 3H), 2.22 (quint, J=7.2 Hz, 2H), 1.86 (t, J=2.4 Hz, 3H).

EXAMPLE 2(274)8-(N-propyl-N-(5-methylfuran-2-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.89 (dd, J=2.7, 8.4 Hz, 1H), 5.99 (d, J=3.0 Hz, 1H), 5.85 (dd, J=1.6,3.0 Hz, 1H), 4.78 (s, 2H), 3.84 (s, 3H), 3.35 (m, 2H), 2.90 (t, J=7.5Hz, 2H), 2.81 (t, J=7.2 Hz, 2H), 2.39 (s, 3H), 2.22 (m, 3H), 2.07 (m,2H), 1.62 (m, 2H), 0.91 (t, J=7.5 Hz, 3H).

EXAMPLE 2(275)8-(N-benzyl-N-cyclopropylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.42–7.30 (m, 4H), 7.25–7.15 (m, 2H), 7.09 (d,J=2.4 Hz, 1H), 7.00–6.94 (m, 1H), 5.39 (d, J=14.7 Hz, 1H), 5.27 (d,J=14.7 Hz, 1H), 3.85 (s, 3H), 3.70–3.32 (m, 2H), 3.12 (m, 2H), 2.96 (m,1H), 2.37 (s, 3H), 2.21 (m, 2H), 1.20–0.92 (m, 4H).

EXAMPLE 2(276)8-(N-benzyl-N-cyclopropylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.30–7.26 (m, 3H),7.15–7.09 (m, 2H), 7.08 (d, J=2.4 Hz, 1H), 6.91 (dd, J=8.4, 2.4 Hz, 1H),5.20 (s, 2H), 5.19 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H),2.41 (s, 3H), 0.92–0.78 (m, 4H).

EXAMPLE 2(277)8-(N-benzyl-N-cyclopropylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33–7.19 (m, 3H), 7.19 (d, J=8.1 Hz, 1H),7.14–7.08 (m, 2H), 6.88 (d, J=2.7 Hz, 1H), 6.82 (dd, J=8.1, 2.7 Hz, 1H),5.32–5.12 (m, 2H), 5.19 (s, 2H), 4.89 (s, 2H), 3.83 (s, 3H), 2.57 (m,1H), 2.38 (s, 3H), 2.18 (s, 3H), 0.92–0.78 (m, 4H).

EXAMPLE 2(278)8-(N-cyclopropylmethyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.30 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.33 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.94 (dd, J=8.4, 2.4 Hz, 1H), 5.30 (m) and 5.27 (s) total 4H, 4.32 (m,2H), 3.84 (s, 3H), 3.72–3.67 (m, 4H), 3.31 (s, 3H), 2.36 (s, 3H), 1.11(m, 1H), 0.71 (m, 2H), 0.36 (m, 2H).

EXAMPLE 2(279)8-(N-cyclopropylmethyl-N-(2-methoxyethyl)amino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.33 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.95 (dd, J=8.4, 2.4 Hz, 1H), 4.30 (m, 2H), 3.85 (s, 3H), 3.71 (d, J=6.6Hz, 2H), 3.64 (t, J=5.1 Hz, 2H), 3.41 (m, 2H), 3.29 (s, 3H), 3.07 (t,J=7.2 Hz, 2H), 2.34 (s, 3H), 2.24 (quint, J=7.2 Hz, 2H), 1.09 (m, 1H),0.65 (m, 2H), 0.31 (m, 2H).

EXAMPLE 2(280)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-bromophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.65 (d, J=2.1 Hz, 1H), 7.44 (dd, J=2.1, 8.1 Hz,1H), 7.28 (d, J=8.1 Hz, 1H), 6.23 (br d, J=10.5 Hz, 1H), 3.81 (m, 1H),3.09 (t, J=7.2 Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.34 (s, 3H), 2.15 (m,2H), 1.60–1.82 (m, 4H), 1.01 (t, J=7.5 Hz, 6H).

EXAMPLE 2(281)8-(3-pentylamino)-2-methyl-3-(2,5-dichloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.65 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.40 (s, 1H), 7.06 (s, 1H), 6.22 (br d, J=10.5Hz, 1H), 3.92 (s, 3H), 3.81 (m, 1H), 3.08 (t, J=6.9 Hz, 2H), 2.91 (t,J=7.8 Hz, 1H), 2.33 (s, 3H), 2.15 (m, 2H), 1.58–1.82 (m, 4H), 1.01 (t,J=7.5 Hz, 6H).

EXAMPLE 2(282)8-(3-pentylamino)-2-methyl-3-(2,5-dichloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.39 (s, 1H), 7.07 (s, 1H), 6.34 (br d, J=10.5Hz, 1H), 5.29 (m, 2H), 4.93 (m, 2H), 3.93 (s, 3H), 3.24 (m, 1H), 2.36(s, 3H), 1.67–1.84 (m, 4H), 1.02 (t, J=7.2 Hz, 6H).

EXAMPLE 2(283)8-(N-cyclopropyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.61 (d, J=7.8 Hz, 2H), 7.33 (d, J=7.8 Hz, 2H),7.30 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H), 6.91 (dd, J=8.7, 2.7 Hz,1H), 5.27 (s, 2H), 5.25 (s, 2H), 4.93 (s, 2H), 3.84 (s, 3H), 2.58 (m,1H), 2.40 (s, 3H), 0.84 (m, 4H).

EXAMPLE 2(284)8-(N-cyclopropyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.24 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.61 (d, J=7.8 Hz, 2H), 7.33 (d, J=7.8 Hz, 2H),7.17 (d, J=8.1 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H), 6.82 (dd, J=8.1, 2.7 Hz,1H), 5.40–5.20 (m, 2H), 5.25 (s, 2H), 4.91 (s, 2H), 3.83 (s, 3H), 2.58(m, 1H), 2.36 (s, 3H), 2.17 (s, 3H), 0.84 (m, 4H).

EXAMPLE 2(285)8-dibutylamino-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.66 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.1 Hz, 1H),6.94 (dd, J=8.4, 2.1 Hz, 1H), 3.84 (s and m, total 7H), 3.35 (m, 2H),3.01 (t, J=7.5 Hz, 2H), 2.33 (s, 3H), 2.22 (quint, J=7.5 Hz, 2H), 1.67(quint, J=7.5 Hz, 4H), 1.36 (sixt, J=7.5 Hz, 2H), 0.95 (t, J=7.5 Hz,6H).

EXAMPLE 2(286)8-dibutylamino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.63 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.11 (d, J=8.4 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H),6.83 (dd, J=8.4, 2.4 Hz, 1H), 5.43 (s, 2H), 5.21 (s, 2H), 3.88 (m, 4H),3.83 (s, 3H), 2.29 (s, 3H), 2.20 (s, 3H), 1.78 (quint, J=7.5 Hz, 4H),1.42 (sixt, J=7.5 Hz, 4H), 1.00 (t, J=7.5 Hz, 6H).

EXAMPLE 2(287)8-bis(2-methoxyethyl)amino-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (d, J=9.0 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H),6.96 (dd, J=9.0, 2.7 Hz, 1H), 4.15 (m, 4H), 3.85 (s, 3H), 3.64 (t, J=5.4Hz, 4H), 3.53 (m, 1H), 3.45 (m, 1H), 3.31 (s, 6H), 3.05 (t, J=7.2 Hz,2H), 2.34 (s, 3H), 2.22 (quint, J=7.2 Hz, 2H).

EXAMPLE 2(288)8-(N-ethyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=7.8 Hz, 1H), 7.07 (d, J=2.1 Hz, 1H),6.92 (m, 1H), 5.28 (s, 2H), 5.11 (s, 2H), 3.84 (s, 3H), 3.81 (m, 2H),3.69 (m, 2H), 2.37 (s, 3H), 1.33 (s, 3H), 1.09 (m, 1H), 0.60 (m, 2H),0.24 (m, 2H).

EXAMPLE 2(289)8-(N-ethyl-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.12 (m, 1H), 6.89 (s, 1H), 6.82 (m, 1H), 5.38(m, 2H), 5.31 (m, 2H), 3.99 (m, 2H), 3.83 (s and m, total 5H), 2.31 (s,3H), 2.20 (s, 3H), 1.44 (m, 3H), 1.19 (m, 1H), 0.72 (m, 2H), 0.36 (m,2H).

EXAMPLE 2(290)8-(N-ethyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 3.84 (s, 3H), 3.77 (q, J=7.2 Hz, 2H), 3.59(d, J=6.6 Hz, 2H), 3.04 (t, J=7.5 Hz, 4H), 2.36 (s, 3H), 2.16 (quint,J=7.5 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H), 1.03 (m, 1H), 0.50 (m, 2H), 0.15(m, 2H).

EXAMPLE 2(291)8-(N-cyclopropyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.29 (hexane:ethyl acetate=2:1);

NMR (300 MHz, DMSO-d₆): δ 7.83–7.76 (m, 2H), 7.54–7.48 (m, 2H), 7.30(dd, J=8.7, 1.2 Hz, 1H), 7.16 (m, 1H), 7.02–6.96 (m, 1H), 5.12 (m, 2H),3.82 (s, 3H), 3.06 (m, 2H), 2.94–2.78 (m, 3H), 2.25 (s, 3H), 2.05 (m,2H), 0.79–0.70 (m, 2H), 0.61 (m, 2H).

EXAMPLE 2(292)8-(N-cyclopropylmethyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.37 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.69 (brd, J=7.2 Hz, 2H), 7.49 (brd, J=7.2 Hz,2H), 7.34 (brd, J=8.4 Hz, 1H), 7.09 (d, J=2.1 Hz, 1H), 6.96 (m, 1H),5.33 (m, 2H), 3.85 (s, 3H), 3.60 (m, 2H), 3.48 (m, 2H), 3.10 (m, 2H),2.33 (s, 3H), 2.28 (m, 2H), 1.18–1.02 (m, 1H), 0.70–0.58 (m, 2H),0.22–0.10 (m, 2H).

EXAMPLE 2(293)8-(N-cyclopropylmethyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.21 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.68 (d, J=8.1 Hz, 2H), 7.52 (d, J=8.1 Hz, 2H),7.31 (d, J=8.7 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H), 6.94 (dd, J=8.7, 2.4 Hz,1H), 5.26 (m, 4H), 5.14 (s, 2H), 3.84 (s, 3H), 3.45 (d, J=6.6 Hz, 2H),2.36 (s, 3H), 1.05 (m, 1H), 0.68–0.56 (m, 2H), 0.18–0.10 (m, 2H).

EXAMPLE 2(294)8-(N-cyclopropylmethyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.37 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.66 (d, J=7.8 Hz, 2H), 7.52 (d, J=7.8 Hz, 2H),7.15 (d, J=8.1 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H), 6.82 (dd, J=8.1, 2.4 Hz,1H), 5.25 (s, 2H), 5.13 (s, 2H), 5.00 (s, 2H), 3.83 (s, 3H), 3.41 (d,J=6.6 Hz, 2H), 2.34 (s, 3H), 2.18 (s, 3H), 1.02 (m, 1H), 0.60–0.52 (m,2H), 0.12–0.06 (m, 2H).

EXAMPLE 2(295)8-(N-propyl-N-(thiophen-3-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.7 Hz, 1H), 7.28 (m, 1H), 7.13 (m,1H), 7.08 (d, J=2.4 Hz, 1H), 6.98 (dd, J=0.9, 4.8 Hz, 1H), 6.90 (dd,J=2.4, 8.7 Hz, 1H), 5.08 (s, 2H), 4.96 (s, 2H), 4.89 (s, 2H), 3.84 (s,3H), 3.32 (m, 2H), 2.41 (s, 3H), 1.64 (m, 2H), 0.90 (t, J=7.5 Hz, 3H).

EXAMPLE 2(296)8-(N-propyl-N-(5-methylthiophen-2-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.7 Hz, 1H), 7.07 (d, J=2.4 Hz, 1H),6.90 (dd, J=2.4, 8.7 Hz, 1H), 6.66 (d, J=3.3 Hz, 1H), 6.56 (m, 1H),5.02–5.17 (m, 4H), 4.90 (s, 2H), 3.84 (s, 3H), 3.27 (m, 2H), 2.44 (s,3H), 2.42 (s, 3H), 1.64 (m, 2H), 0.92 (t, J=7.5 Hz, 3H).

EXAMPLE 2(297)8-(N-butyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.1 Hz, 1H),6.89 (dd, J=8.7, 2.1 Hz, 1H), 3.83 (s, 3H), 3.69 (t, J=7.2 Hz, 2H), 3.56(d, J=7.2 Hz, 2H), 3.02 (m, 4H), 2.36 (s, 3H), 2.15 (quint, J=7.2 Hz,2H), 1.58 (quint, J=7.5 Hz, 2H), 1.34 (sixt, J=7.5 Hz, 2H), 1.02 (m,1H), 0.91 (t, J=7.5 Hz, 3H), 0.48 (m, 2H), 0.13 (m, 2H).

EXAMPLE 2(298)8-(N-butyl-N-cyclopropylmethylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.1 Hz, 1H),6.93 (dd, J=8.4, 2.1 Hz, 1H), 5.25 (s, 2H), 5.17 (s, 2H), 3.84 (s, 3H),3.77 (m, 2H), 3.71 (m, 2H), 2.37 (s, 3H), 1.70 (quint, J=7.2 Hz, 2H),1.39 (sixt, J=7.2 Hz, 2H), 1.10 (m, 1H), 0.96 (t, J=7.2 Hz, 3H), 0.62(m, 2H), 0.25 (m, 2H).

EXAMPLE 2(299)8-(N-butyl-N-cyclopropylmethylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.7 Hz, 1H), 6.88 (d, J=2.1 Hz, 1H),6.81 (dd, J=8.7, 2.1 Hz, 1H), 5.25 (s, 2H), 5.13 (s, 2H), 3.83 (s, 3H),3.75 (m, 2H), 3.70 (m, 2H), 2.33 (s, 3H), 2.18 (s, 3H), 1.69 (m, 2H),1.39 (sixt, J=7.5 Hz, 2H), 1.09 (m, 1H), 0.96 (t, J=7.5 Hz, 3H), 0.60(m, 2H), 0.23 (m, 2H).

EXAMPLE 2(300)8-(N-propyl-N-(thiophen-3-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.28 (dd, J=2.7, 5.1 Hz, 1H), 7.18 (d, J=8.7 Hz,1H), 7.13 (m, 1H), 6.97 (dd, J=1.5, 5.1 Hz, 1H), 6.88 (d, J=3.0 Hz, 1H),6.81 (dd, J=3.0, 8.7 Hz, 1H), 5.07 (s, 2H), 4.96 (s, 2H), 4.87 (s, 2H),3.83 (s, 3H), 3.31 (m, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 1.64 (m, 2H),0.91 (t, J=7.2 Hz, 3H).

EXAMPLE 2(301)8-(N-propyl-N-(5-methylthiophen-2-yl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.18 (d, J=8.4 Hz, 1H), 6.88 (d, J=3.0 Hz, 1H),6.81 (dd, J=3.0, 8.4 Hz, 1H), 6.65 (d, J=3.3 Hz, 1H), 6.55 (m, 1H), 5.11(s, 4H), 4.88 (s, 2H), 3.83 (s, 3H), 3.27 (m, 2H), 2.43 (s, 3H), 2.38(s, 3H), 2.19 (s, 3H), 1.65 (m, 2H), 0.92 (t, J=7.5 Hz, 3H).

EXAMPLE 2(302)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-ethoxycarbonylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.56 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.21 (d, J=1.5 Hz, 1H), 8.08 (dd, J=1.5, 7.8 Hz,1H), 7.56 (d, J=7.8 Hz, 1H), 7.30 (brd, J=10.8 Hz, 1H), 4.38 (q, J=6.9Hz, 2H), 4.00 (m, 1H), 3.34–3.64 (m, 2H), 3.15 (t, J=6.9 Hz, 2H), 2.35(s, 3H), 2.31 (m, 2H), 1.65–1.96 (m, 4H), 1.41 (t, J=6.9 Hz, 3H), 1.07(t, J=7.5 Hz, 3H), 1.06 (t, J=7.5 Hz, 3H).

EXAMPLE 2(303)8-(N-propyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.35 (m, 2H), 7.10–6.92 (m, 5H), 5.16 (m, 2H),3.85 (s, 3H), 3.70 (m, 2H), 3.60–3.34 (m, 2H), 3.03 (m, 2H), 2.35 (s,3H), 2.26 (m, 2H), 1.75 (m, 2H), 0.94 (m, 3H).

EXAMPLE 2(304)8-(N-propyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.48–7.33 (m, 2H), 7.13–7.04 (m, 4H), 6.97 (dd,J=8.4, 2.4 Hz, 1H), 5.50–5.15 (m, 4H), 5.17 (s, 2H), 3.85 (s, 3H),3.74–3.60 (m, 2H), 2.37 (s, 3H), 1.82 (sext, J=7.2 Hz, 2H), 0.97 (t,J=7.2 Hz, 3H).

EXAMPLE 2(305)8-(N-propyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.36–7.26 (m, 1H), 7.16 (d, J=8.7 Hz, 1H),7.09–6.96 (m, 3H), 6.88 (d, J=2.7 Hz, 1H), 6.82 (dd, J=8.7, 2.7 Hz, 1H),5.13 (s, 2H), 5.03 (s, 2H), 5.02 (s, 2H), 3.83 (s, 3H), 3.41 (m, 2H),2.35 (s, 3H), 2.19 (s, 3H), 1.69 (sext, J=7.2 Hz, 2H), 0.92 (t, J=7.2Hz, 3H).

EXAMPLE 2(306)8-(N-propyl-N-(5-methylthiophen-2-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.89 (dd, J=2.7, 8.4 Hz, 1H), 6.64 (d, J=3.3 Hz, 1H), 6.54 (m, 1H), 4.96(s, 2H), 3.84 (s, 3H), 3.38 (m, 2H), 2.90 (t, J=7.5 Hz, 2H), 2.86 (t,J=7.2 Hz, 2H), 2.43 (s, 3H), 2.40 (s, 3H), 2.08 (m, 2H), 1.61 (m, 2H),0.90 (t, J=7.5 Hz, 3H).

EXAMPLE 2(307)8-(N-propyl-N-(thiophen-3-yl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.7 Hz, 1H), 7.25 (m, 1H), 7.11 (m,1H), 7.07 (d, J=2.7 Hz, 1H), 6.95 (dd, J=1.5, 5.1 Hz, 1H), 6.89 (dd,J=2.7, 8.7 Hz, 1H), 4.85 (s, 2H), 3.84 (s, 3H), 3.39 (m, 2H), 2.90 (t,J=7.5 Hz, 2H), 2.81 (t, J=7.2 Hz, 2H), 2.39 (s, 3H), 2.07 (m, 2H), 1.60(m, 2H), 0.89 (t, J=7.2 Hz, 3H).

EXAMPLE 2(308)8-(N-ethyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.88 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 3.66 (q, J=6.9 Hz, 2H),3.60–3.50 (m, 2H), 3.02–2.84 (m, 4H), 2.37 (s, 3H), 2.20–2.04 (m, 2H),1.64–1.52 (m, 2H), 1.17 (t, J=6.9 Hz, 3H), 0.90 (t, J=6.9 Hz, 3H).

EXAMPLE 2(309)8-(N-ethyl-N-propylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.7 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.80 (dd, J=8.7, 2.7 Hz, 1H), 5.20 (s, 2H), 4.89 (s, 2H), 3.82 (s, 3H),3.67 (q, J=7.2 Hz, 2H), 3.60–3.48 (m, 2H), 2.34 (s, 3H), 2.18 (s, 3H),1.72–1.56 (m, 2H), 1.23 (t, J=7.2 Hz, 3H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 2(310)8-(N-ethyl-N-propylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.89 (dd, J=8.7, 2.7 Hz, 1H), 5.19 (s, 2H), 4.90 (s, 2H), 3.83 (s, 3H),3.67 (q, J=7.2 Hz, 2H), 3.60–3.48 (m, 2H), 2.38 (s, 3H), 1.70–1.50 (m,2H), 1.24 (t, J=7.2 Hz, 3H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 2(311)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-carbamoylphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (methylene chloride:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.96 (d, J=1.8 Hz, 1H), 7.70 (dd, J=8.1, 1.8 Hz,1H), 7.50 (d, J=8.1 Hz, 1H), 6.26 (d, J=10.5 Hz, 1H), 3.82 (m, 1H),3.14–3.05 (m, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.36 (s, 3H), 2.22–2.10 (m,2H), 1.85–1.50 (m, 4H), 1.02 (t, J=7.5 Hz, 6H).

EXAMPLE 2(312)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-(N-methylcarbamoyl)phenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (methylene chloride:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.89 (d, J=1.8 Hz, 1H), 7.64 (dd, J=7.8, 1.8 Hz,1H), 7.45 (d, J=7.8 Hz, 1H), 6.42 (brs, 1H), 6.26 (d, J=10.2 Hz, 1H),3.82 (m, 1H), 3.14–3.05 (m, 2H), 3.01 (d, J=4.5 Hz, 3H), 2.91 (t, J=7.8Hz, 2H), 2.35 (s, 3H), 2.22–2.09 (m, 2H), 1.82–1.55 (m, 4H), 1.02 (t,J=7.5 Hz, 6H).

EXAMPLE 2(313)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-(N,N-dimethylcarbamoyl)phenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.65 (methylene chloride:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.56 (d, J=1.5 Hz, 1H), 7.46 (d, J=7.8 Hz, 1H),7.36 (dd, J=7.8, 1.5 Hz, 1H), 6.26 (d, J=9.9 Hz, 1H), 3.82 (m, 1H),3.17–3.02 (m, 8H), 2.92 (t, J=7.8 Hz, 2H), 2.34 (s, 3H), 2.21–2.06 (m,2H), 1.85–1.42 (m, 4H), 1.02 (t, J=7.5 Hz, 6H).

EXAMPLE 2(314)8-(3-pentylamino)-2-methyl-3-(2,6-dimethyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.29 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 6.69 (s, 2H), 6.32 (d, J=10.8 Hz, 1H), 5.29 (s,2H), 4.88 (s, 2H), 3.80 (s, 3H), 3.30–3.18 (m, 1H), 2.22 (s, 3H), 2.04(s, 6H), 1.83–1.55 (m, 4H), 1.03 (t, J=7.2 Hz, 6H).

EXAMPLE 2(315)8-(N-ethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30–7.22 (m, 2H), 7.18 (d, J=8.1 Hz, 1H),7.06–6.94 (m, 2H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=8.1, 2.7 Hz, 1H),5.09 (s, 2H), 4.96–4.80 (m, 4H), 3.83 (s, 3H), 3.41 (q, J=7.2 Hz, 2H),2.37 (s, 3H), 2.18 (s, 3H), 1.23 (t, J=7.2 Hz, 3H).

EXAMPLE 2(316)8-(N-ethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.26–7.22 (m, 2H), 7.07(d, J=2.4 Hz, 1H), 7.04–6.94 (m, 2H), 6.90 (dd, J=8.4, 2.4 Hz, 1H), 4.81(s, 2H), 3.84 (s, 3H), 3.47 (q, J=7.2 Hz, 2H), 2.90 (t, J=7.2 Hz, 2H),2.82 (t, J=7.2 Hz, 2H), 2.40 (s, 3H), 2.16–1.98 (m, 2H), 1.18 (t, J=7.2Hz, 3H).

EXAMPLE 2(317)8-(N-ethyl-N-(4-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.31 (d, J=8.1 Hz, 1H), 7.30–7.24 (m, 2H), 7.08(d, J=2.7 Hz, 1H), 7.06–6.94 (m, 2H), 6.91 (dd, J=8.1, 2.7 Hz, 1H), 5.10(s, 2H), 4.90 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.42 (q, J=7.2 Hz,2H), 2.40 (s, 3H), 1.22 (t, J=7.2 Hz, 3H).

EXAMPLE 2(318)8-(3-pentylamino)-2-methyl-3-(2-chloro-4,6-dimethoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 6.67 (d, J=2.7 Hz, 1H), 6.45 (d, J=2.7 Hz, 1H),6.23 (d, J=10.8 Hz, 1H), 3.82 (s, 3H), 3.80 (m, 1H), 3.70 (s, 3H), 3.07(m, 2H), 2.90 (m, 2H), 2.25 (s, 3H), 2.13 (m, 2H), 1.52–1.80 (m, 4H),1.02 (t, J=7.2 Hz, 3H), 1.01 (t, J=7.2 Hz, 3H).

EXAMPLE 2(319)8-(3-pentylamino)-2-methyl-3-(2-chloro-4,6-dimethoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.22 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): 6.68 (d, J=2.7 Hz, 1H), 6.47 (d, J=2.7 Hz, 1H),6.34 (d, J=10.8 Hz, 1H), 5.28 (s, 2H), 4.92 (d, J=13.5 Hz, 1H), 4.90 (d,J=13.5 Hz, 1H), 3.83 (s, 3H), 3.71 (s, 3H), 3.23 (m, 1H), 2.28 (s, 3H),1.53–1.82 (m, 4H), 1.02 (t, J=7.5 Hz, 3H), 1.01 (t, J=7.5 Hz, 3H).

EXAMPLE 2(320)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-aminophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.82 (d, J=2.1 Hz, 1H),6.63 (dd, J=8.4, 2.1 Hz, 1H), 6.21 (d, J=10.2 Hz, 1H), 3.87–3.62 (m,3H), 3.12–3.03 (m, 2H), 2.95–2.86 (m, 2H), 2.34 (s, 3H), 2.20–2.07 (m,2H), 1.85–1.50 (m, 4H), 1.01 (t, J=7.5 Hz, 6H).

EXAMPLE 2(321)8-(4-heptylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.7 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.7, 2.7 Hz, 1H), 6.32 (d, J=10.8 Hz, 1H), 5.29 (s, 2H),4.90 (s, 2H), 3.82 (s, 3H), 3.40 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H),1.78–1.38 (m, 8H), 0.95 (t, J=7.2 Hz, 6H).

EXAMPLE 2(322)8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methylaminophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.18 (d, J=8.4 Hz, 1H), 6.73 (d, J=2.4 Hz, 1H),6.56 (dd, J=8.4, 2.4 Hz, 1H), 6.21 (d, J=10.5 Hz, 1H), 3.88–3.70 (m,2H), 3.12–3.02 (m, 2H), 2.95–2.80 (m, 2H), 2.85 (s, 3H), 2.34 (s, 3H),2.20–2.05 (m, 2H), 1.80–1.50 (m, 4H), 1.01 (t, J=7.2 Hz, 6H).

EXAMPLE 2(323)8-(3-pentylamino)-2-methyl-3-(2-formyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.26 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 9.85 (s, 1H), 7.55 (d, J=2.7 Hz, 1H), 7.38 (d,J=8.4 Hz, 1H), 7.22 (dd, J=8.4, 2.7 Hz, 1H), 6.23 (d, J=9.6 Hz, 1H),3.93–3.74 (m) and 3.89 (s) total 4H, 3.09 (t, J=7.5 Hz, 2H), 2.88 (t,J=7.5 Hz, 2H), 2.39 (s, 3H), 2.14 (quint, J=7.5 Hz, 2H), 1.83–1.50 (m,4H), 1.02 (t, J=7.5 Hz, 6H).

EXAMPLE 2(324)8-(3-pentylamino)-2-methyl-3-(2-cyano-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.46 (d, J=9.0 Hz, 1H), 7.24 (d, J=2.4 Hz, 1H),7.18 (dd, J=9.0, 2.4 Hz, 1H), 6.24 (d, J=10.5 Hz, 1H), 3.88–3.73 (m) and3.86 (s) total 4H, 3.09 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.2 Hz, 2H), 2.43(s, 3H), 2.15 (quint, J=7.2 Hz, 2H), 1.80–1.50 (m, 4H), 1.02 (t, J=7.2Hz, 6H).

EXAMPLE 2(325)8-(3-pentylamino)-2-methyl-3-(2-ethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.12 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H),6.77 (dd, J=8.4, 2.4 Hz, 1H), 6.21 (d, J=10.5 Hz, 1H), 3.83–3.75 (m) and3.83 (s) total 4H, 3.08 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.2 Hz, 2H), 2.52(q, J=7.8 Hz, 2H), 2.28 (s, 3H), 2.13 (quint, J=7.2 Hz, 2H), 1.83–1.50(m, 4H), 1.10–0.98 (m, 9H).

EXAMPLE 2(326)8-(4-heptylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.51 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.20 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.38 (d,J=10.2 Hz, 1H), 7.08–6.97 (m, 2H), 4.15 (m, 1H), 3.84 (s, 3H), 3.61 (m,2H), 3.16 (m, 2H), 2.33 (m, 2H), 1.88–1.60 (m, 4H), 1.60–1.35 (m, 4H),0.99 (t, J=7.5 Hz, 6H).

EXAMPLE 2(327)8-(N,N-dipropylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.32 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.03 (d,J=2.7 Hz, 1H), 6.91 (dd, J=8.7, 2.7 Hz, 1H), 3.83 (s, 3H), 3.57 (m, 4H),2.97 (m, 4H), 2.17 (m, 2H), 1.66–1.50 (m, 4H), 0.88 (t, J=7.5 Hz, 6H).

EXAMPLE 2(328)8-(N,N-dipropylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.35 (s, 1H), 7.72 (d, J=9.0 Hz, 1H), 7.04 (d,J=2.4 Hz, 1H), 6.91 (dd, J=9.0, 2.4 Hz, 1H), 5.20 (s, 2H), 4.94 (s, 2H),3.82 (s, 3H), 3.57 (t, J=7.5 Hz, 4H), 1.72–1.46 (m, 4H), 0.90 (t, J=7.2Hz, 6H).

EXAMPLE 2(329)8-(N-cyclopropylmethyl-N-propylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.60 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.05 (d,J=2.7 Hz, 1H), 6.92 (dd, J=8.4, 2.7 Hz, 1H), 5.25 (s, 2H), 4.96 (s, 2H),3.83 (s, 3H), 3.64–3.50 (m, 4H), 1.72–1.56 (m, 2H), 1.04 (m, 1H), 0.93(t, J=7.5 Hz, 3H), 0.58–0.44 (m, 2H), 0.20–0.08 (m, 2H).

EXAMPLE 2(330)8-(N-benzyl-N-cyclopropylmethylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.42 (s, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.38–7.20(m, 5H), 7.06 (d, J=2.7 Hz, 1H), 6.93 (dd, J=8.4, 2.7 Hz, 1H), 5.25 (s,2H), 4.96 (s, 2H), 4.95 (s, 2H), 3.84 (s, 3H), 3.43 (d, J=6.6 Hz, 2H),1.04 (m, 1H), 0.58–0.46 (m, 2H), 0.16–0.04 (m, 2H).

EXAMPLE 2(331)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.56 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.42 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.19 (d,J=7.8 Hz, 2H), 7.13 (d, J=7.8 Hz, 2H), 7.06 (d, J=2.4 Hz, 1H), 6.93 (dd,J=8.4, 2.4 Hz, 1H), 5.24 (s, 2H), 4.95 (s, 2H), 4.91 (s, 2H), 3.84 (s,3H), 3.42 (d, J=6.3 Hz, 2H), 2.33 (s, 3H), 1.04 (m, 1H), 0.58–0.46 (m,2H), 0.18–0.04 (m, 2H).

EXAMPLE 2(332)8-(N-propyl-N-(2-butynyl)amino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.41 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.05 (d,J=2.7 Hz, 1H), 6.92 (dd, J=8.7, 2.7 Hz, 1H), 5.34 (s, 2H), 4.97 (s, 2H),4.44 (q, J=2.4 Hz, 2H), 3.83 (s, 3H), 3.52 (m, 2H), 1.82 (t, J=2.4 Hz,3H), 1.80–1.62 (m, 2H), 0.98 (t, J=7.2 Hz, 3H).

EXAMPLE 2(333)8-(3-pentylamino)-2-methyl-3-(2-methoxycarbonyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.70 (d, J=2.7 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H),7.30–7.16 (m) and 7.19 (dd, J=8.4, 2.7 Hz) total 2H, 4.03–3.83 (m) and3.89 (s) total 4H, 3.77 (s, 3H), 3.54–3.36 (m, 2H), 3.11 (t, J=7.5 Hz,2H), 2.33–2.00 (m) and 2.25 (s) total 4H, 1.90–1.58 (m, 4H), 1.05 (t,J=7.5 Hz, 6H).

EXAMPLE 2(334)8-(N-butyl-N-cyclopropylmethylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.05 (d,J=2.7 Hz, 1H), 6.91 (dd, J=9.0, 2.7 Hz, 1H), 5.25 (s, 2H), 4.96 (s, 2H),3.83 (s, 3H), 3.66–3.52 (m, 4H), 1.66–1.48 (m, 2H), 1.44–1.22 (m, 2H),1.04 (m, 1H), 0.91 (t, J=7.2 Hz, 3H), 0.60–0.44 (m, 2H), 0.22–0.08 (m,2H).

EXAMPLE 2(335)8-(3-pentylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.57 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.32 (s, 1H), 7.74 (d, J=8.7 Hz, 1H), 7.04 (d,J=2.7 Hz, 1H), 6.91 (dd, J=8.7, 2.7 Hz, 1H), 6.42 (d, J=10.8 Hz, 1H),5.31 (s, 2H), 4.97 (s, 2H), 3.83 (s, 3H), 3.28 (m, 1H), 1.84–1.54 (m,4H), 1.01 (t, J=7.2 Hz, 6H).

EXAMPLE 2(336)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.41 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.41 (s, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.38–7.24(m, 2H), 7.12–6.96 (m, 3H), 6.92 (dd, J=9.0, 2.7 Hz, 1H), 5.25 (s, 2H),4.95 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 3.39 (d, J=6.9 Hz, 2H), 1.02(m, 1H), 0.60–0.44 (m, 2H), 0.16–0.02 (m, 2H).

EXAMPLE 2(337)8-(N-cyclopropyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.41 (toluene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.4 Hz, 1H), 7.23 (m, 1H), 7.13–6.97(m, 3H), 7.06 (d, J=2.7 Hz, 1H), 6.89 (dd, J=8.4, 2.7 Hz, 1H), 5.15(brs, 2H), 3.84 (s, 3H), 2.98–2.86 (m, 4H), 2.83 (m, 1H), 2.40 (s, 3H),2.02 (m, 2H), 0.84–0.72 (m, 4H).

EXAMPLE 2(338)8-(N-cyclopropylmethyl-N-(2-fluorophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.49 (toluene:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.7 Hz, 1H), 7.35–7.16 (m, 2H), 7.06(d, J=2.4 Hz, 1H), 7.08–6.97 (m, 2H), 6.89 (dd, J=8.7 Hz, 2.4 Hz, 1H),5.02 (s, 2H), 3.84 (s, 3H), 3.41 (d, J=6.9 Hz, 2H), 2.98–2.84 (m, 4H),2.40 (s, 3H), 2.07 (m, 2H), 1.05 (m, 1H), 0.48 (m, 2H), 0.10 (m, 2H).

EXAMPLE 2(339)8-(N-cyclopropylmethyl-N-propylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.76 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.32 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.03 (d,J=2.7 Hz, 1H), 6.91 (dd, J=8.7, 2.7 Hz, 1H), 3.83 (s, 3H), 3.68–3.58 (m,2H), 3.52 (d, J=6.9 Hz, 2H), 3.06–2.90 (m, 4H), 2.26–2.08 (m, 2H),1.66–1.46 (m, 2H), 1.01 (m, 1H), 0.90 (t, J=7.2 Hz, 3H), 0.52–0.42 (m,2H), 0.16–0.04 (m, 2H).

EXAMPLE 2(340)8-(N-propyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.79 (d, J=9.0 Hz, 1H), 7.18–7.07(m, 4H), 7.04 (d, J=2.7 Hz, 1H), 6.92 (dd, J=9.0, 2.7 Hz, 1H), 4.79 (s,2H), 3.83 (s, 3H), 3.45–3.36 (m, 2H), 2.96 (t, J=7.8 Hz, 2H), 2.89 (t,J=7.8 Hz, 2H), 2.32 (s, 3H), 2.20–2.04 (m, 2H), 1.66–1.46 (m, 2H), 0.87(t, J=7.2 Hz, 3H).

EXAMPLE 2(341)8-(N-benzyl-N-cyclopropylmethylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.67 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.38 (s, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.38–7.18(m, 5H), 7.05 (d, J=2.4 Hz, 1H), 6.92 (dd, J=8.7, 2.4 Hz, 1H), 4.92 (s,2H), 3.83 (s, 3H), 3.40 (d, J=6.9 Hz, 2H), 3.01 (t, J=7.2 Hz, 2H), 2.97(t, J=7.8 Hz, 2H), 2.22–2.06 (m, 2H), 1.02 (m, 1H), 0.54–0.42 (m, 2H),0.12–0.02 (m, 2H).

EXAMPLE 2(342)8-(N-cyclopropylmethyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.71 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.20 (d,J=8.1 Hz, 2H), 7.11 (d, J=8.1 Hz, 2H), 7.05 (d, J=2.7 Hz, 1H), 6.92 (dd,J=8.4, 2.7 Hz, 1H), 4.88 (s, 2H), 3.83 (s, 3H), 3.39 (d, J=6.6 Hz, 2H),3.01 (t, J=7.2 Hz, 2H), 2.97 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.22–2.06(m, 2H), 1.02 (m, 1H), 0.54–0.42 (m, 2H), 0.14–0.02 (m, 2H).

EXAMPLE 2(343)8-(N-propyl-N-(4-fluorophenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.30–7.22(m, 2H), 7.05 (d, J=2.4 Hz, 1H), 7.04–6.96 (m, 2H), 6.92 (dd, J=8.7, 2.4Hz, 1H), 4.78 (s, 2H), 3.83 (s, 3H), 3.46–3.34 (m, 2H), 2.97 (t, J=7.8Hz, 2H), 2.89 (t, J=7.2 Hz, 2H), 2.20–2.04 (m, 2H), 1.66–1.48 (m, 2H),0.87 (t, J=7.5 Hz, 3H).

EXAMPLE 2(344)8-dicyclopropylmethylamino-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.28 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.03 (d,J=2.4 Hz, 1H), 6.91 (dd, J=8.7, 2.4 Hz, 1H), 6.42 (d, J=9.6 Hz, 1H),3.82 (s, 3H), 3.44 (m, 1H), 3.10–3.00 (m, 2H), 2.98–2.88 (m, 2H),2.22–2.06 (m, 2H), 1.20–1.06 (m, 2H), 0.68–0.48 (m, 4H), 0.48–0.34 (m,4H).

EXAMPLE 2(345)8-(4-heptylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.32 (s, 1H), 7.74 (d, J=8.7 Hz, 1H), 7.04 (d,J=2.7 Hz, 1H), 6.92 (dd, J=8.7, 2.7 Hz, 1H), 6.42 (d, J=10.8 Hz, 1H),5.32 (s, 2H), 4.97 (s, 2H), 3.83 (s, 3H), 3.42 (m, 1H), 1.78–1.26 (m,8H), 0.95 (t, J=7.2 Hz, 6H).

EXAMPLE 2(346)8-(N-propyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.41 (s, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.16–7.08(m, 4H), 7.06 (d, J=2.4 Hz, 1H), 6.92 (dd, J=8.7, 2.4 Hz, 1H), 5.14 (s,2H), 4.95 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.42–3.28 (m, 2H), 2.33(s, 3H), 1.72–1.50 (m, 2H), 0.89 (t, J=7.5 Hz, 3H).

EXAMPLE 2(347)8-(N-propyl-N-(4-fluorophenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.41 (s, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.32–7.18(m, 2H), 7.08–6.97 (m, 3H), 6.93 (dd, J=8.4, 2.4 Hz, 1H), 5.15 (s, 2H),4.95 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.40–3.26 (m, 2H), 1.70–1.48(m, 2H), 0.89 (t, J=7.2 Hz, 3H).

EXAMPLE 2(348)8-dicyclopropylmethylamino-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.47 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.33 (s, 1H), 7.73 (d, J=8.7 Hz, 1H), 7.04 (d,J=2.7 Hz, 1H), 6.91 (dd, J=8.7, 2.7 Hz, 1H), 6.55 (d, J=9.6 Hz, 1H),5.25 (s, 2H), 4.94 (s, 2H), 3.83 (s, 3H), 2.92 (m, 1H), 1.22–1.06 (m,2H), 0.70–0.48 (m, 4H), 0.48–0.30 (m, 4H).

EXAMPLE 2(349)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.41 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.60 (d,J=8.1 Hz, 2H), 7.50 (d, J=8.1 Hz, 2H), 7.06 (d, J=2.7 Hz, 1H), 6.93 (dd,J=8.4, 2.7 Hz, 1H), 5.27 (s, 2H), 5.02 (s, 2H), 4.96 (s, 2H), 3.84 (s,3H), 3.40 (d, J=6.6 Hz, 2H), 1.02 (m, 1H), 0.60–0.46 (m, 2H), 0.16–0.04(m, 2H).

EXAMPLE 2(350)8-(N-cyclopropyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.60 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.36 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.12–6.99(m, 5H), 6.93 (dd, J=8.4, 2.7 Hz, 1H), 4.96 (s, 2H), 3.83 (s, 3H), 2.97(t, J=7.8 Hz, 2H), 2.94 (t, J=7.5 Hz, 2H), 2.78 (m, 1H), 2.32 (s, 3H),2.16–2.00 (m, 2H), 0.82–0.68 (m, 4H).

EXAMPLE 2(351)8-(N-cyclopropylmethyl-N-(4-trifluoromethylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.58 (d,J=8.1 Hz, 2H), 7.49 (d, J=8.1 Hz, 2H), 7.05 (d, J=2.7 Hz, 1H), 6.92 (dd,J=8.7, 2.7 Hz, 1H), 4.97 (s, 2H), 3.83 (s, 3H), 3.39 (d, J=6.6 Hz, 2H),3.04 (t, J=7.2 Hz, 2H), 2.99 (t, J=7.8 Hz, 2H), 2.18 (m, 2H), 1.01 (m,1H), 0.56–0.42 (m, 2H), 0.14–0.02 (m, 2H).

EXAMPLE 2(352)8-(3-pentylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.27 (s, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.03 (d,J=2.4 Hz, 1H), 6.91 (dd, J=8.7, 2.4 Hz, 1H), 6.30 (d, J=10.2 Hz, 1H),3.82 (s, 3H), 3.82 (m, 1H), 3.11 (t, J=7.2 Hz, 2H), 2.96 (t, J=7.8 Hz,2H), 2.24–2.08 (m, 2H), 1.84–1.52 (m, 4H), 1.01 (t, J=7.5 Hz, 6H).

EXAMPLE 2(353)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.37 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.38–7.24(m, 2H), 7.05 (d, J=2.7 Hz, 1H), 7.05–6.93 (m, 2H), 6.92 (dd, J=8.7, 2.7Hz, 1H), 4.87 (s, 2H), 3.83 (s, 3H), 3.37 (d, J=6.9 Hz, 2H), 3.01 (t,J=7.5 Hz, 2H), 2.97 (t, J=7.5 Hz, 2H), 2.22–2.06 (m, 2H), 1.00 (m, 1H),0.54–0.40 (m, 2H), 0.12–0.02 (m, 2H).

EXAMPLE 2(354)8-(3-pentylamino)-2-methyl-3-(2-(1−methyl-1-hydroxyethyl)-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (hexane:ethyl acetate=1:2);

NMR (300 MHz, CDCl₃): δ 7.23 (d, J=2.7 Hz, 1H), 7.03 (d, J=8.7 Hz, 1H),6.83 (dd, J=8.7, 2.7 Hz, 1H), 6.26 (d, J=10.2 Hz, 1H), 5.00–4.85 (m,1H), 3.85–3.75 (m) and 3.84 (s) total 4H, 3.06 (t, J=6.9 Hz, 2H), 2.85(t, J=6.9 Hz, 2H), 2.29 (s, 3H), 2.11 (quint, J=7.5 Hz, 2H), 1.80–1.50(m) and 1.64 (s) total 7H, 1.30 (s, 3H), 1.03 (t, J=7.2 Hz) and 1.00 (t,J=7.2 Hz) total 6H.

EXAMPLE 2(355)8-(N-propyl-N-(4-trifluoromethyloxyphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=9.0 Hz, 2H), 7.32 (d, J=8.4 Hz, 1H),7.15 (d, J=9.0 Hz, 2H), 7.07 (d, J=2.7 Hz, 1H), 6.89 (dd, J=8.4, 2.7 Hz,1H), 4.84 (s, 2H), 3.84 (s, 3H), 3.44–3.32 (m, 2H), 2.91 (t, J=7.5 Hz,2H), 2.84 (t, J=7.8 Hz, 2H), 2.39 (s, 3H), 2.06–1.98 (m, 2H), 1.66–1.48(m, 2H), 0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 2(356)8-(3-hexylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30 (d, J=8.7 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H),6.88 (dd, J=8.7, 2.4 Hz, 1H), 6.22 (d, J=10.8 Hz, 1H), 3.84 (m, 1H),3.83 (s, 3H), 3.08 (t, J=7.5 Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.34 (s,3H), 2.20–2.04 (m, 2H), 1.80–1.32 (m, 6H), 1.00 (t, J=6.9 Hz, 3H), 0.95(t, J=6.9 Hz, 3H).

EXAMPLE 2(357)8-(3-pentylamino)-2-methyl-3-(2-methoxy-4-methylpyridin-5-yl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.23 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.00 (s, 1H), 6.69 (s, 1H), 6.23 (d, J=10.5 Hz,1H), 3.94 (s, 3H), 3.82 (m, 1H), 3.08 (t, J=7.5 Hz, 2H), 2.89 (t, J=7.8Hz, 2H), 2.32 (s, 3H), 2.20–2.06 (m, 2H), 2.18 (s, 3H), 1.82–1.54 (m,4H), 1.02 (t, J=7.2 Hz, 6H).

EXAMPLE 2(358)8-(N-butyl-N-cyclopropylmethylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.27 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.04 (d,J=2.4 Hz, 1H), 6.94 (m, 1H), 3.90–3.70 (m, 2H), 3.83 (s, 3H), 3.64 (d,J=6.6 Hz, 2H), 3.30–3.12 (m, 2H), 3.12–2.96 (m, 2H), 2.32–2.12 (m, 2H),1.68–1.50 (m, 2H), 1.46–1.20 (m, 2H), 1.06 (m, 1H), 0.91 (t, J=7.2 Hz,3H), 0.62–0.46 (m, 2H), 0.24–0.10 (m, 2H).

EXAMPLE 2(359)8-(N-cyclopropyl-N-(4-methylphenyl)methylamino)-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 8.42 (s, 1H), 7.76 (d, J=8.7 Hz, 1H), 7.09 (d,J=8.1 Hz, 2H), 7.06 (d, J=2.7 Hz, 1H), 6.99 (d, J=8.1 Hz, 2H), 6.93 (dd,J=8.7, 2.7 Hz, 1H), 5.19 (s, 2H), 5.11 (s, 2H), 4.96 (s, 2H), 3.84 (s,3H), 2.58 (m, 1H), 2.32 (s, 3H), 0.86–0.76 (m, 4H).

EXAMPLE 2(360)8-(N-propyl-N-(4-methylphenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.74 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.32 (d, J=8.7 Hz, 1H), 7.16–7.06 (m, 4H), 7.07(d, J=3.0 Hz, 1H), 6.89 (dd, J=8.7, 3.0 Hz, 1H), 4.80 (s, 2H), 3.84 (s,3H), 3.42–3.30 (m, 2H), 2.89 (t, J=7.8 Hz, 2H), 2.82 (t, J=7.2 Hz, 2H),2.39 (s, 3H), 2.33 (s, 3H), 2.04–1.98 (m, 2H), 1.70–1.48 (m, 2H), 0.87(t, J=7.2 Hz, 3H).

EXAMPLE 2(361)8-(N-propyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.64 (d, J=8.1 Hz, 2H), 7.50 (d, J=8.1 Hz, 2H),7.30 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.7 Hz, 1H), 6.90 (d, J=8.4, 2.7 Hz,1H), 5.14 (s, 2H), 5.01 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 3.36–3.22(m, 2H), 2.38 (s, 3H), 1.70–1.50 (m, 2H), 0.89 (t, J=7.2 Hz, 3H).

EXAMPLE 2(362)8-(N-propyl-N-(4-cyanophenyl)methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.61 (d, J=7.8 Hz, 2H), 7.47 (d, J=7.8 Hz, 2H),7.31 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H), 6.89 (dd, J=8.4, 2.7 Hz,1H), 4.90 (s, 2H), 3.84 (s, 3H), 3.44–3.32 (m, 2H), 2.92 (t, J=7.8 Hz,2H), 2.88 (t, J=7.5 Hz, 2H), 2.38 (s, 3H), 2.20–2.02 (m, 2H), 1.66–1.46(m, 2H), 0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 2(363)8-(N-cyclopropylmethyl-N-methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.30 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.30 (d, J=8.4 Hz, 1H), 7.05 (d, J=3.0 Hz, 1H),6.88 (dd, J=8.4, 3.0 Hz, 1H), 3.83 (s, 3H), 3.61 (d, J=6.9 Hz, 2H), 3.30(s, 3H), 3.12 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H), 2.36 (s, 3H),2.20–2.06 (m, 2H), 1.09 (m, 1H), 0.60–0.46 (m, 2H), 0.24–0.12 (m, 2H).

EXAMPLE 2(364)8-(N-cyclopropylmethyl-N-methylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.22 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.87 (d, J=3.0 Hz, 1H),6.80 (dd, J=8.4, 3.0 Hz, 1H), 5.35 (s, 2H), 4.89 (s, 2H), 3.83 (s, 3H),3.72 (dd, J=6.9, 1.5 Hz, 2H), 3.27 (s, 3H), 2.34 (s, 3H), 2.15 (s, 3H),1.10 (m, 1H), 0.60–0.48 (m, 2H), 0.24–0.14 (m, 2H).

EXAMPLE 2(365)8-(N-cyclopropylmethyl-N-methylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.88 (dd, J=8.7, 2.7 Hz, 1H), 5.35 (s, 2H), 4.91 (s, 2H), 3.83 (s, 3H),3.71 (d, J=6.9 Hz, 2H), 3.27 (s, 3H), 2.38 (s, 3H), 1.10 (m, 1H),0.62–0.50 (m, 2H), 0.26–0.16 (m, 2H).

EXAMPLE 2(366)8-(4-heptylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.80 (s, 1H), 6.83 (s, 2H), 6.27 (d, J=11.1 Hz,1H), 3.98 (m, 1H), 3.80 (s, 3H), 3.11 (t, J=7.5 Hz, 2H), 2.91 (t, J=7.8Hz, 2H), 2.22–2.04 (m, 2H), 2.13 (s, 6H), 1.76–1.30 (m, 8H), 0.96 (t,J=7.2 Hz, 6H).

EXAMPLE 2(367)8-dipropylamino-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.86 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H),3.64–3.46 (m, 4H), 2.98 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H),2.22–2.00 (m, 2H), 2.12 (s, 6H), 1.68–1.48 (m, 4H), 0.89 (t, J=7.5 Hz,6H).

EXAMPLE 2(368)8-(N-cyclopropylmethyl-N-propylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.86 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H),3.68–3.58 (m, 2H), 3.54 (d, J=6.6 Hz, 2H), 3.03 (t, J=7.5 Hz, 2H), 2.93(t, J=7.5 Hz, 2H), 2.04–2.00 (m, 2H), 2.12 (s, 6H), 1.68–1.50 (m, 2H),1.02 (m, 1H), 0.91 (t, J=7.5 Hz, 3H), 0.54–0.40 (m, 2H), 0.18–0.04 (m,2H).

EXAMPLE 2(369)8-(N-benzyl-N-cyclopropylmethylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.49 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.93 (s, 1H), 7.42–7.08 (m, 5H), 6.70 (s, 2H),4.94 (s, 2H), 3.81 (s, 3H), 3.41 (d, J=6.6 Hz, 2H), 3.02 (t, J=7.5 Hz,2H), 2.92 (t, J=7.8 Hz, 2H), 2.22–2.04 (m, 2H), 2.13 (s, 6H), 1.03 (m,1H), 0.54–0.38 (m, 2H), 0.12–0.01 (m, 2H).

EXAMPLE 2(370)8-(N-cyclopropylmethyl-N-(4-methylphenylmethyl)amino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.53 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.92 (s, 1H), 7.21 (d, J=8.1 Hz, 2H), 7.11 (d,J=8.1 Hz, 2H), 6.70 (s, 2H), 4.89 (s, 2H), 3.81 (s, 3H), 3.40 (d, J=6.9Hz, 2H), 3.02 (t, J=7.2 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H), 2.32 (s, 3H),2.22–2.04 (m, 2H), 2.13 (s, 6H), 1.03 (m, 1H), 0.54–0.40 (m, 2H),0.10–0.01 (m, 2H).

EXAMPLE 2(371)8-(N-propyl-N-(4-fluorophenylmethyl)amino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.92 (s, 1H), 7.36–7.18 (m, 2H), 7.06–6.88 (m,2H), 6.70 (s, 2H), 4.80 (s, 2H), 3.81 (s, 3H), 3.46–3.32 (m, 2H),3.00–2.80 (m, 4H), 2.22–2.00 (m, 2H), 2.13 (s, 6H), 1.70–1.48 (m, 2H),0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 2(372)8-dicyclopropylmethylamino-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.81 (s, 1H), 6.68 (s, 2H), 6.40 (d, J=9.9 Hz,1H), 3.80 (s, 3H), 3.46 (m, 1H), 3.05 (t, J=7.5 Hz, 2H), 2.89 (t, J=7.8Hz, 2H), 2.22–2.02 (m, 2H), 2.13 (s, 6H), 1.20–1.06 (m, 2H), 0.68–0.36(m, 8H).

EXAMPLE 2(373)8-(N-butyl-N-cyclopropylmethylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.61 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.87 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H),3.76–3.60 (m, 2H), 3.53 (d, J=6.9 Hz, 2H), 3.03 (t, J=7.2 Hz, 2H), 2.93(t, J=7.5 Hz, 2H), 2.22–2.00 (m, 2H), 2.12 (s, 6H), 1.64–1.46 (m, 2H),1.42–1.22 (m, 2H), 1.02 (m, 1H), 0.90 (t, J=7.2 Hz, 3H), 0.56–0.38 (m,2H), 0.18–0.02 (m, 2H).

EXAMPLE 2(374)8-(N-cyclopropylmethyl-N-(4-fluorophenyl)methylamino)-3-(2,6-dimethyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[ci]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.92 (s, 1H), 7.38–7.26 (m, 2H), 7.06–6.94 (m,2H), 6.71 (s, 2H), 4.89 (s, 2H), 3.81 (s, 3H), 3.39 (d, J=6.6 Hz, 2H),3.02 (t, J=7.2 Hz, 2H), 2.93 (t, J=7.2 Hz, 2H), 2.22–2.00 (m, 2H), 2.13(s, 6H), 1.01 (m, 1H), 0.54–0.40 (m, 2H), 0.10–0.01 (m, 2H).

EXAMPLE 38-(N-ethyl-N-n-butylamino)-2-hydroxymethyl-3-(2-methyl-4-hydroxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 2(1) (506 mg) inmethylene chloride (14 ml) which was cooled to −78° C., 1M borontribromide in methylene chloride (12 ml) was added. The mixture wasstirred for 30 minutes at −78° C. and for 5 hours at −30° C. Thereaction mixture was poured into a saturated aqueous solution of sodiumbicarbonate and the resultant solution was extracted with ethyl acetate.The organic layer was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(n-hexane:ethyl acetate=1:1→2:3) to give the title compound (303 mg)having the following physical data

TLC: Rf 0.14 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 9.41 (brs, 1H), 6.90 (d, J=9.0 Hz, 1H), 6.42 (m,2H), 4.71 (brs, 2H), 3.70 (q, J=7.5 Hz, 2H), 3.64 (t, J=7.5 Hz, 2H),3.01 (t, J=7.8 Hz, 4H), 2.39 (brs, 1H), 2.18 (m, 2H), 2.01 (s, 3H), 1.58(m, 2H), 1.35 (m, 2H), 1.21 (t, J=7.5 Hz, 3H), 0.91 (t, J=7.5 Hz, 3H).

EXAMPLE 48-(N-ethyl-N-n-butylamino)-2-hydroxymethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 3 (985 mg) inmethylene chloride (10 ml) which was cooled to 0° C., sodium hydride (95mg; 63.1% dispersion in oil) was added. The mixture was stirred for 30minutes. Methyl iodide (0.18 ml) was added to the reaction mixture, andthe resultant mixture was stirred for 2 hours at 0° C. A saturatedaqueous solution of ammonium chloride was added to the reaction mixture,and the resultant solution was extracted with ethyl acetate. The organiclayer was washed with 1M aqueous solution of sodium hydroxide and asaturated aqueous solution of sodium chloride, successively, dried overanhydrous sodium sulfate and concentrated. The residue was purified bycolumn chromatography on silica gel (toluene:ethyl acetate=5:1→4:1→7:2)to give the title compound (947 mg) having the following physical data.

TLC: Rf 0.35 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.19 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.78 (dd, J=8.4, 2.7 Hz, 1H), 4.73 (d, J=5.7 Hz, 2H), 3.82 (s, 3H), 3.65(q, J=7.2 Hz, 2H), 3.59 (t, J=7.2 Hz, 2H), 2.98 (t, J=6.9 Hz, 2H), 2.92(t, J=7.8 Hz, 2H), 2.35 (m, 1H), 2.19 (s, 3H), 2.15 (m, 2H), 1.55 (m,2H), 1.35 (m, 2H), 1.18 (t, J=7.2 Hz, 3H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 58-(N-propyl-N-(2-methoxyiminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 2(2) (186 mg) indimethylsulfoxide (5 ml), triethylamine (0.39 ml) and sulfur trioxidepyridine complex (225 mg) were added. The mixture was stirred for 2hours at room temperature. The reaction mixture was poured into waterand extracted with ethyl acetate. The organic layer was washed with asaturated aqueous solution of sodium chloride, dried over anhydroussodium sulfate and concentrated. To a solution of the residue inpyridine (5 ml), o-methylhydroxylamine hydrochloride (28 mg) was added.The mixture was stirred for 15 hours at room temperature. The reactionmixture was concentrated and diluted with ethyl acetate. The dilutedsolution was washed with a saturated aqueous solution of sodiumbicarbonate and a saturated aqueous solution of sodium chloride,successively, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(n-hexane:ethyl acetate=4:1→3:1) to give the title compound (16 mg)having the following physical data.

TLC: Rf 0.78 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃):

Major Isomer

δ 7.57 (t, J=5.7 Hz, 1H), 7.15 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.4 Hz,1H), 6.79 (dd, J=8.4, 2.4 Hz, 1H), 4.35 (d, J=6.0 Hz, 2H), 3.86 (s, 3H),3.82 (s, 3H), 3.49 (t, J=7.8 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H), 2.91 (t,J=7.5 Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.14 (m, 2H), 1.58 (m, 2H),0.90 (t, J=7.2 Hz, 3H)

Minor Isomer

δ 7.15 (d, J=8.4 Hz, 1H), 6.95 (t, J=3.9 Hz, 1H), 6.86 (d, J=2.4 Hz,1H), 6.79 (dd, J=8.4, 2.4 Hz, 1H), 4.47 (d, J=4.2 Hz, 2H), 3.90 (s, 3H),3.82 (s, 3H), 3.54 (t, J=7.8 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H), 2.91 (t,J=7.5 Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.14 (m, 2H), 1.58 (m, 2H),0.92 (t, J=7.2 Hz, 3H).

EXAMPLE 5(1)–5(2)

The following compounds were obtained by the same procedure as areaction of Example 5, using the compound prepared in Example 2(26), orthe compound prepared in Example 4 and hydroxylamine hydrochlorideinstead of o-methylhydroxylamine hydrochloride.

EXAMPLE 5(1)8-(N-propyl-N-(2-methoxyiminoethyl)amino)-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.22 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, pyridine-d₅ 0.5 ml+CDCl₃ 0.1 ml):

Major Isomer

δ 7.87 (t, J=5.4 Hz, 1H), 7.38 (d, J=8.4 Hz, 1H), 7.03 (d, J=2.7 Hz,1H), 6.95 (dd, J=8.4, 2.7 Hz, 1H), 5.27 (s, 2H), 4.97 (s, 2H), 4.59 (d,J=5.4 Hz, 2H), 3.86 (s, 3H), 3.74 (s, 3H), 3.38 (t, J=7.5 Hz, 2H), 2.44(s, 3H), 2.31 (s, 3H), 1.65–1.50 (m, 2H), 0.81 (t, J=7.5 Hz, 3H).

Minor Isomer

δ 7.38 (d, J=8.4 Hz, 1H), 7.31 (t, J=4.2 Hz, 1H), 7.03 (d, J=2.7 Hz,1H), 6.95 (dd, J=8.4, 2.7 Hz, 1H), 5.25 (s, 2H), 4.95 (s, 2H), 4.71 (d,J=4.2 Hz, 2H), 3.92 (s, 3H), 3.74 (s, 3H), 3.43 (t, J=7.2 Hz, 2H), 2.43(s, 3H), 2.31 (s, 3H), 1.65–1.50 (m, 2H), 0.84 (t, J=7.2 Hz, 3H).

EXAMPLE 5(2)8-(N-ethyl-N-n-butylamino)-2-hydroxyiminomethyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.19 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.15 (s, 1H), 7.96 (brs, 1H), 7.18 (d, J=8.1 Hz,1H), 6.85 (d, J=2.7 Hz, 1H), 6.79 (dd, J=8.1, 2.7 Hz, 1H), 3.82 (s, 3H),3.67 (q, J=7.2 Hz, 2H), 3.61 (t, J=7.5 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H),2.92 (t, J=7.8 Hz, 2H), 2.18 (s, 3H), 2.16 (m, 2H), 1.55 (m, 2H), 1.33(m, 2H), 1.18 (t, J=7.2 Hz, 3H), 0.89 (t, J=7.5 Hz, 3H).

EXAMPLE 68-[(2S)-1-hydroxyiminobutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 2(15) (290 mg) inacetic acid (4 ml), 1M hydrochloric acid (1.4 ml) was added, and themixture was stirred for 1 hour at 80° C. The reaction mixture was pouredinto a saturated aqueous solution of sodium bicarbonate (100 ml) underice-bath, the resultant mixture was extracted with ethyl acetate. Theorganic layer was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated.Hydroxylamine hydrochloride (52 mg) was added to a solution of theresidue in pyridine (3 ml), and the mixture was stirred for 15 hours atroom temperature. The reaction mixture was concentrated, and dilutedwith ethyl acetate. The diluted solution was washed with a saturatedaqueous solution of sodium bicarbonate and a saturated aqueous solutionof sodium chloride, successively, dried over anhydrous sodium sulfateand concentrated. The residue was purified by column chromatography onsilica gel (n-hexane:ethyl acetate=1:1) to give the title compound (143mg) having the following physical data as isomeric mixtures.

TLC: Rf 0.32 (n-hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃):

Major Isomer

δ 7.80 (brs, 1H), 7.47 (d, J=6.0 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.84(d, J=2.7 Hz, 1H), 6.78 (dd, J=8.4, 2.7 Hz, 1H), 6.53 (d, J=9.6 Hz, 1H),4.60 (m, 1H), 3.82 (s, 3H), 3.25–3.00 (m, 2H), 2.88 (t, J=7.5 Hz, 2H),2.31 (s, 3H), 2.17 (s, 3H), 2.10 (m, 2H), 1.90 (m, 2H), 1.11 (t, J=7.2Hz, 3H),

Minor Isomer

δ 8.52 (brs, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.84 (d, J=2.7 Hz, 1H), 6.80(m, 1H), 6.78 (dd, J=8.4, 2.7 Hz, 1H), 6.44 (d, J=9.6 Hz, 1H), 5.23 (m,1H), 3.82 (s, 3H), 3.25–3.00 (m, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.31 (s,3H), 2.17 (s, 3H), 2.10 (m, 2H), 1.90 (m, 2H), 1.11 (t, J=7.2 Hz, 3H).

EXAMPLE 6(1)8-[(2S)-1-methoxyiminobutan-2-yl]amino-2-methyl-3-(2-methyl-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

The title compound (128 mg) having the following physical data wasobtained by the same procedure as a reaction of Example 5, using thecompound prepared in Example 2(14) (365 mg) and o-methylhydroxylaminehydrochloride instead of hydroxylamine hydrochloride.

TLC: Rf 0.20 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃):

Major Isomer

δ 7.36 (d, J=6.0 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz,1H), 6.79 (dd, J=8.4, 2.7 Hz, 1H), 6.60 (d, J=9.9 Hz, 1H), 5.47 (d,J=10.5 Hz, 1H), 5.31 (d, J=10.5 Hz, 1H), 4.89 (s, 2H), 4.07 (m, 1H),3.86 (s, 3H), 3.82 (s, 3H), 2.33 (s, 3H), 2.16 (s, 3H), 1.96–1.87 (m,2H), 1.10 (t, J=7.5 Hz, 3H).

Minor Isomer

δ 7.14 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H), 6.79 (dd, J=8.4, 2.7Hz, 1H), 6.76 (m, 1H), 6.53 (d, J=9.9 Hz, 1H), 5.30 (m, 2H), 4.89 (s,2H), 4.72 (m, 1H), 3.96 (s, 3H), 3.82 (s, 3H), 2.33 (s, 3H), 2.16 (s,3H), 1.96–1.87 (m, 2H), 1.10 (t, J=7.5 Hz, 3H).

EXAMPLE 78-[(1S)-1-cyanopropylamino]-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 6 (137 mg) inmethylene chloride (1 ml) which was cooled to −78° C., triethylamine(0.32 ml) and trifluoromethanesulfonic anhydride (0.13 ml) were added.The mixture was stirred for 2 hours at room temperature. A saturatedaqueous solution of sodium bicarbonate was added to the reactionmixture, and the resultant solution was extracted with ethyl acetate.The organic layer was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous sodium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(n-hexane:ethyl acetate=3:1→2:1) to give the title compound (100 mg)having the following physical data.

TLC: Rf 0.27 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃) δ 7.15 (d, J=8.1 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.79 (dd, J=8.1, 2.7 Hz, 1H), 6.50 (d, J=9.6 Hz, 1H), 4.78 (m, 1H), 3.82(s, 3H), 3.33 (ddd, J=14.4, 7.5, 6.3 Hz, 1H), 3.11 (ddd, J=14.4, 8.1,6.3 Hz, 1H), 2.93 (m, 2H), 2.31 (s, 3H), 2.25–2.10 (m, 7H), 1.29 (t,J=7.5 Hz, 3H).

EXAMPLE 7(1)8-(N-ethyl-N-n-butylamino)-2-cyano-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

The title compound (195 mg) having the following physical data wasobtained by the same procedure as a reaction of Example 7, using thecompound prepared in Example 5(2) (211 mg).

TLC: Rf 0.34 (n-hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H),6.83 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 3.65 (q, J=6.9 Hz, 2H), 3.58(t, J=7.5 Hz, 2H), 3.00 (t, J=7.2 Hz, 2H), 2.96 (t, J=7.8 Hz, 2H), 2.29(s, 3H), 2.18 (m, 2H), 1.57 (m, 2H), 1.33 (m, 2H), 1.20 (t, J=6.9 Hz,3H), 0.91 (t, J=7.2 Hz, 3H).

EXAMPLE 89-(3-pentylamino)-6-methyl-5-(2-methyl-4-methoxyphenyl)-furo[3,2-d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 2(6) (215 mg) indiphenyl ether (3 ml), 10% palladium carbon (150 mg) was added, and themixture was stirred for 4 hours at 250° C. After the reaction mixturewas cooled to room temperature, it was diluted with methanol (10 ml).The diluted solution was filtered though celite (registered trademark).The filtrate was concentrated, and the residue was purified by columnchromatography on silica gel (n-hexane:acetone=9:1) to give the titlecompound (150 mg) having the following physical data.

TLC: Rf 0.42 (n-hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.76 (d, J=2.4 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H),6.88 (d, J=2.7 Hz, 1H), 6.80 (dd, J=8.1, 2.7 Hz, 1H), 6.78 (d, J=2.4 Hz,1H), 6.28 (brd, J=10.2 Hz, 1H), 4.30 (m, 1H), 3.83 (s, 3H), 2.37 (s,3H), 2.21 (s, 3H), 1.92–1.65 (m, 4H), 1.05 (m, 6H).

EXAMPLE 98-(3-pentyloxy)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

3-Pentanol (202 mg) was dropped into a solution of sodium hydride (92.0mg; 60% in oil) in toluene, and the mixture was stirred for 2 minutes at80° C. The compound prepared in Reference example 7 (250 mg) was addedto this mixture, and the resultant mixture was stirred for 5 hours.Water and ethyl acetate were added to the reaction mixture and stirred.The organic layer was separated. Meanwhile, the water layer wasextracted with ethyl acetate. A combined organic layer was washed with asaturated aqueous solution of sodium chloride, dried over anhydroussodium sulfate and concentrated. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate=5:1) to give thetitle compound (128 mg) having the following physical data.

TLC: Rf 0.58 (toluene:acetone=5:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H),6.79 (dd, J=8.4, 2.4 Hz, 1H), 5.05 (quint, J=6.0 Hz, 1H), 3.82 (s, 3H),3.05 (t, J=7.5 Hz, 2H), 2.94 (t, J=7.5 Hz, 2H), 2.34 (s, 3H), 2.22–2.10(m, 2H), 2.16 (s, 3H), 1.92–1.78 (m, 4H), 1.05 (t, J=7.5 Hz, 6H).

EXAMPLE 9(1)–9(5)

The following compounds were obtained by the same procedure as areaction of Example 9, using a corresponding compound.

EXAMPLE 9(1)8-(3-pentyloxy)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 5.06 (quint, J=6.0 Hz, 1H), 3.83 (s, 3H),3.05 (t, J=7.2 Hz, 2H), 2.95 (t, J=7.2 Hz, 2H), 2.38 (s, 3H), 2.16(quint, J=7.2 Hz, 2H), 1.94–1.74 (m, 4H), 1.04 (t, J=7.5 Hz, 6H).

EXAMPLE 9(2)8-(3-pentyloxy)-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.25 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.7 Hz, 1H),6.90 (dd, J=8.4, 2.7 Hz, 1H), 5.29 (s, 2H), 4.93 (s, 2H), 4.56 (m, 1H),3.84 (s, 3H), 2.41 (s, 3H), 1.99–1.80 (m, 4H), 1.05 (t, J=7.5 Hz, 6H).

EXAMPLE 9(3)8-(4-heptyloxy)-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.85 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.89 (dd, J=8.7, 2.7 Hz, 1H), 5.22 (quint, J=6.0 Hz, 1H), 3.83 (s, 3H),3.05 (t, J=7.5 Hz, 2H), 2.95 (t, J=7.5 Hz, 2H), 2.37 (s, 3H), 2.16(quint, J=7.5 Hz, 2H), 1.90–1.66 (m, 4H), 1.58–1.42 (m, 4H), 0.95 (t,J=7.2 Hz, 6H).

EXAMPLE 9(4)8-isopropyloxy-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 5.43 (sept, J=6.3 Hz, 1H), 3.83 (s, 3H),3.06 (t, J=7.5 Hz, 2H), 2.96 (t, J=7.5 Hz, 2H), 2.38 (s, 3H), 2.16(quint, J=7.5 Hz, 2H), 1.51 (d, J=6.3 Hz, 6H).

EXAMPLE 9(5)8-(1,6-heptadien-4-yl)oxy-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.4 Hz, 1H), 7.06 (d, J=2.7 Hz, 1H),6.89 (dd, J=8.4, 2.7 Hz, 1H), 5.90 (ddt, J=17.1, 10.2, 6.9 Hz, 2H), 5.34(quint, J=6.3 Hz, 1H), 5.17 (m, 2H), 5.11 (dd, m, 2H), 3.83 (s, 3H),3.01 (t, J=7.5 Hz, 2H), 2.95 (t, J=7.5 Hz, 2H), 2.70–2.50 (m, 4H), 2.38(s, 3H), 2.15 (quint, J=7.5 Hz, 2H).

EXAMPLE 108-(3-pentylthio)-2-methyl-3-(2-chloro-5-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

3-Acetylthiopentane (252 mg) and the compound prepared in Referenceexample 7 (300 mg) were added to a solution of sodium hydride (68.9 mg;60% in oil) in ethanol (17 ml) at 0° C. After the mixture was stirredfor 1 hour, the reaction mixture was concentrated. Water and ethylacetate were added to the residue and stirred. The organic layer wasseparated. Meanwhile, the water layer was extracted with ethyl acetate.A combined organic layer was washed with a saturated aqueous solution ofsodium chloride, dried over anhydrous sodium sulfate and concentrated.The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=5:1) 4N hydrochloric acid—ethyl acetate (0.2 ml)was added to the purified matter, and the solution was stirred for 10minutes and concentrated to give the title compound (271.1 mg) havingthe following physical data.

TLC: Rf 0.57 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.29 (d, J=8.7 Hz, 1H), 7.07 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.7, 2.4 Hz, 1H), 4.27 (quint, J=6.3 Hz, 1H), 3.84 (s, 3H),3.05 (t, J=7.5 Hz, 2H), 3.00 (t, J=7.5 Hz, 2H), 2.40 (s, 3H), 2.17(quint, J=7.5 Hz, 2H), 1.72–1.64 (m, 4H), 1.02 (t, J=7.5 Hz, 6H).

EXAMPLE 118-(4-methylphenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To the compound prepared in Reference example 7 (300 mg) indimethoxyethane (3 ml), 4-methylphenylboronic acid (131 mg), palladiumacetate (11 mg), triphenylphosphine (48 mg) and a saturated aqueoussolution of sodium carbonate (2 ml) were added, and the mixture wasrefluxed with heating for 5 hours. After the reaction mixture wascooled, it was diluted with ethyl acetate. The diluted solution waswashed with a saturated aqueous solution of sodium chloride and water,dried over anhydrous magnesium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (hexane:ethylacetate=5:1) to give the title compound (222 mg) having the followingphysical data.

TLC: Rf 0.41 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.72 (d, J=8.1 Hz, 2H), 7.36 (d, J=8.1 Hz, 2H),7.19 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.4 Hz,1H), 3.84 (s, 3H), 3.01 (t, J=7.5 Hz, 2H), 2.94 (t, J=6.6 Hz, 2H), 2.45(s, 3H), 2.30 (s, 3H), 2.20 (s, 3H), 2.14 (m, 2H).

EXAMPLE 11(1)–11(5)

The following compounds were obtained by the same procedure as areaction of Example 11, using a corresponding compound.

EXAMPLE 11(1)8-(2,4-dichlorophenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf TLC: Rf 0.38 (hexane:ethyl acetate=3:1);

NMR (300 MHz, DMSO-d₆): δ 7.91 (d, J=1.8 Hz, 1H), 7.70 (d, J=8.4 Hz,1H), 7.64 (dd, J=1.8, 8.4 Hz, 1H), 7.11 (br d, J=8.1 Hz, 1H), 6.90 (d,J=2.7 Hz, 1H), 6.81 (dd, J=2.7, 8.4 Hz, 1H), 3.77 (s, 3H), 2.94 (m, 2H),2.68 (m, 2H), 2.14 (s, 3H), 2.12 (m, 2H), 2.09 (s, 3H).

EXAMPLE 11(2)8-(3-trifluoromethylphenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.27 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.08 (brs, 1H), 8.06 (brd, J=8.1 Hz, 1H), 7.79(brd, J=7.8 Hz, 1H), 7.70 (brdd, J=8.1, 7.8 Hz, 1H), 7.19 (d, J=8.1 Hz,1H), 6.89 (d, J=2.7 Hz, 1H), 6.82 (dd, J=8.1, 2.7 Hz, 1H), 3.84 (s, 3H),3.04 (t, J=7.5 Hz, 2H), 2.94 (t, J=7.5 Hz, 2H), 2.31 (s, 3H), 2.20 (s,3H), 2.18 (m, 2H).

EXAMPLE 11(3)8-(4-methoxyphenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidinehydrochloride

TLC: Rf 0.23 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.92 (d, J=9.0 Hz, 2H), 7.16 (d, J=9.0 Hz, 2H),7.16 (d, J=9.0 Hz, 1H), 6.92 (d, J=2.7 Hz, 1H), 6.86 (dd, J=9.0, 2.7 Hz,1H), 3.95 (s, 3H), 3.85 (s, 3H), 3.61 (t, J=7.5 Hz, 2H), 3.09 (t, J=7.5Hz, 2H), 2.38 (s, 3H), 2.30 (m, 2H), 2.20 (s, 3H).

EXAMPLE 11(4)8-(3,5-dichlorophenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.50 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.69 (d, J=1.8 Hz, 2H), 7.52 (t, J=1.8 Hz, 1H),7.17 (d, J=8.4 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H), 6.82 (dd, J=2.7, 8.4 Hz,1H), 3.84 (s, 3H), 3.02 (t, J=7.5 Hz, 2H), 2.93 (t, J=6.9 Hz, 2H), 2.32(s, 3H), 2.19 (s, 3H), 2.17 (m, 2H).

EXAMPLE 11(5)8-(2-methylphenyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.38 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.34–7.48 (m, 4H), 7.20 (m, 1H), 6.89 (d, J=2.7Hz, 1H), 6.82 (dd, J=2.7, 8.1 Hz, 1H), 3.84 (s, 3H), 3.04 (m, 2H), 2.81(m, 1H), 2.62 (m, 1H), 2.27 (s, 3H), 2.20 (m, 3H), 2.17 (s, 3H), 2.15(m, 2H).

EXAMPLE 128-bis(ethoxycarbonyl)methyl-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

Diethyl malonate (880 mg) was added to a suspension of sodium hydride(210 mg; 63.1% in oil) in tetrahydrofuran (10 ml), and the mixture wasstirred for 30 minutes at room temperature. The compound prepared inReference example 7 (820 mg) was added to the reaction mixture, and theresultant mixture was refluxed with heating for 4 hours. A saturatedaqueous solution of ammonium chloride (10 ml) was added to the reactionmixture, and it was extracted with ethyl acetate. The organic layer waswashed with a saturated aqueous solution of sodium chloride, dried overanhydrous sodium sulfate and concentrated. The residue was purified bycolumn chromatography on silica gel (hexane:ethyl acetate=8:1→7:1) togive the title compound (1.10 g) having the following physical data.

TLC: Rf 0.48 (hexane:ethyl acetate=2:1);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.1 Hz, 1H), 6.87 (d, J=3.0 Hz, 1H),6.80 (dd, J=8.1, 3.0 Hz, 1H), 6.02 (s, 1H), 4.32 (m, 4H), 3.82 (s, 3H),2.96 (t, J=7.8 Hz, 2H), 2.91 (t, J=7.8 Hz, 2H), 2.32 (s, 3H), 2.21–2.09(m, 2H), 2.17 (s, 3H), 1.32 (t, J=7.2 Hz, 6H).

EXAMPLE 12(1)–12(4)

The following compounds were obtained by the same procedure as areaction of Example 12, using a corresponding compound.

EXAMPLE 12(1)8-(1−dimethylamino-1,3-dioxo-2-butyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.55 (ethyl acetate);

NMR (300 MHz, CDCl₃): δ 7.14 (d, J=8.1 Hz, 1H), 6.87 (d, J=1.8 Hz, 1H),6.83–6.74 (m, 1H), 6.29 (s, 1H), 3.83 (s, 3H), 3.05 (s, 3H), 3.05–2.60(m, 6H), 2.41 (s, 3H), 2.30 (s, 3H), 2.16 (brs, 6H).

EXAMPLE 12(2)8-(2,4-dioxo-3-pentyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.34 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 16.93 (s, 1H), 7.19 (d, J=8.4 Hz, 1H), 6.89 (d,J=3.0 Hz, 1H), 6.83 (dd, J=8.4, 3.0 Hz, 1H), 3.84 (s, 3H), 3.04 (t,J=7.2 Hz, 2H), 2.81 (t, J=7.2 Hz, 2H), 2.33 (s, 3H), 2.20 (quint, J=7.2Hz, 2H), 2.18 (s, 3H), 1.95 (s, 6H).

EXAMPLE 12(3)8-bis(ethoxycarbonyl)methyl-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydroH-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.18 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 7.07 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.4, 2.4 Hz, 1H), 6.02 (s, 1H), 4.40–4.20 (m, 4H), 3.84 (s,3H), 2.98 (t, J=7.5 Hz, 2H), 2.92 (t, J=7.5 Hz, 2H), 2.35 (s, 3H), 2.17(quint, J=7.5 Hz, 2H), 1.31 (t, J=7.2 Hz, 6H).

EXAMPLE 12(4)8-bis(ethoxycarbonyl)methyl-2-methyl-3-(2-chloro-4-methoxyphenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[1,5-a]pyrimidine

TLC: Rf 0.28 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.28 (d, J=8.4 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H),6.91 (dd, J=8.4, 2.4 Hz, 1H), 6.12 (s, 1H), 5.11 (s, 2H), 4.95 (s, 2H),4.41–4.20 (m, 4H), 3.84 (s, 3H), 2.39 (s, 3H), 1.33 (t, J=7.2 Hz, 6H).

EXAMPLE 138-(1,3-hydroxy-2-propyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

Under argon atmosphere, 1M diisopropyl aluminium hydride (3.94 ml; inhexane) was dropped into a solution of the compound prepared in Example12 (355 mg) in anhydrous diethyl ether (7 ml) at −78° C. The mixture waswarmed at 0° C. and stirred for 4.5 hours. Methanol was dropped into themixture and then it was warmed at room temperature. 1N hydrochloric acidwas added to the reaction mixture, and the mixture was extracted withethyl acetate. The organic layer was washed with a saturated aqueoussolution of sodium chloride, dried over anhydrous sodium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=3:1) to give the title compound (260mg) having the following physical data.

TLC: Rf 0.50 (chloroform:methanol=9:1);

NMR (300 MHz, CDCl₃): δ 7.13 (brd, J=8.7 Hz, 1H), 6.87 (s, 1H), 6.80(brd, J=8.7 Hz, 1H), 4.97 (m, 1H), 4.90 (m, 1H), 4.24 (m, 2H), 4.13 (m,2H), 3.83 (s, 3H), 3.59 (m, 1H), 2.98 (brt, J=7.2 Hz, 4H), 2.31 (s, 3H),2.28–2.00 (m, 5H).

EXAMPLE 148-(1,3-dimethoxy-2-propyl)-2-methyl-3-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

A solution of the compound prepared in Example 13 (120 mg) in DMF (2 ml)was dropped into a solution of sodium hydride (26.0 mg; 60% in oil) inDMF at 0° C. methyl iodide (81.0 μl) was dropped into the mixture, andthen stirred for 1 hour. Water and ethyl acetate were added to thereaction mixture, and the organic layer was separated. Besides, thewater layer was extracted with ethyl acetate. A combined organic layerwas washed with a saturated aqueous solution of sodium chloride, driedover anhydrous sodium sulfate and concentrated after benzene (5 ml) wasadded. The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=3:1) to give the title compound (58.7 mg) havingthe following physical data.

TLC: Rf 0.80 (ethyl acetate);

NMR (300 MHz, CDCl₃): δ 7.15 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.4 Hz, 1H),6.79 (dd, J=8.4, 2.4 Hz, 1H), 4.28–4.16 (m, 1H), 4.14–4.06 (m, 2H),3.96–3.86 (m, 2H), 3.83 (s, 3H), 3.35 (s, 6H), 3.06 (t, J=7.5 Hz, 2H),2.94 (t, J=7.5 Hz, 2H), 2.31 (s, 3H), 2.17 (s, 3H), 2.17–2.08 (m, 2H).

EXAMPLE 158-(N,N-dimethylcarbamoylmethyl)-2-methyl-3-(2-methyl-4-methyoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine

To a solution of the compound prepared in Example 12 (410 mg) inmethanol (1 ml), 50% aqueous solution of dimethylamino (491 mg) wasadded at 24° C., and the mixture was stirred for 20 hours at 90° C. Thereaction mixture was cooled to room temperature, and water and ethylacetate were added to the mixture and stirred. The organic layer wasseparated. Besides, the water layer was extracted with ethyl acetate.The combined organic layer was washed with a saturated aqueous solutionof sodium chloride, dried over anhydrous sodium sulfate andconcentrated. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=5:1) to give the title compound (102.7mg) having the following physical data.

TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.16 (d, J=8.4 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.80 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 3.27 (d, J=1.2 Hz, 1H),3.04–2.94 (m, 5H), 2.72 (s, 3H), 2.36 (s, 3H), 2.24–2.10 (m, 8H).

REFERENCE EXAMPLE 8 2-chloro-4-methoxybenzaldehyde

To suspension of sodium hydride (2.6 g; 62.6% in oil) indimethylformamide (80 ml), a solution of 2-chloro-4-hydroxybenzaldehyde(10.0 g) in dimethylformamide (50 ml) was dropped over 15 minutes. Themixture was stirred for 30 minutes. Methyl iodide (4.2 ml) was droppedinto the reaction mixture over 10 minutes at 0° C., and stirred for 1hour. The reaction mixture was poured into water and extracted withhexane/ethyl acetate (1:1) The organic layer was washed with water and asaturated aqueous solution of sodium chloride, dried over anhydrousmagnesium sulfate and concentrated to give the title compound (10.7 g)having the following physical data.

TLC: Rf 0.61 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 10.33 (d, J=0.6 Hz, 1H), 7.90 (d, J=9.0 Hz, 1H),6.94 (d, J=2.4 Hz, 1H), 6.89 (ddd, J=9.0, 2.4, 0.6 Hz, 1H), 3.89 (s,3H).

REFERENCE EXAMPLE 9 1-(2,2-dibromoethenyl)-2-chloro-4-methoxybenzene

Carbon tetrabromide (10.7 g) was added to a solution of the compoundprepared in Reference example 8 (5.0 g) in methylene chloride.Triphenylphosphine (16.9 g) was added by portions to the mixturemaintaining inside temperature of 5 degree or less. The mixture wasstirred for 30 minutes at 0° C. A suspension of the reaction mixture inhexane (500 ml) was-poured into silica gel (30 g) and then filtered. Thesilica gel was washed with hexane/ethyl acetate (10:1) The filtrate andwashings were combined and it was concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=10:1) togive the title compound (6.6 g) having the following physical data.

TLC: Rf 0.82 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.62 (d, J=9.0 Hz, 1H), 7.51 (s, 1H), 6.94 (d,J=2.1 Hz, 1H), 6.83 (dd, J=9.0, 2.1 Hz, 1H), 3.81 (s, 3H).

REFERENCE EXAMPLE 10 1-(1-propynyl)-2-chloro-5-methoxybenzene

To a solution of the compound prepared in Reference Example 9 (1.98 g)in tetrahydrofuran (20 ml), 1.57M solution of n-butyl lithium in hexane(8.2 ml) was added at −78° C. The mixture was stirred for 30 minutes and1 hour at 0° C. The reaction mixture was cooled to −78° C., and methyliodide (0.46 ml) was added and stirred for 1 hour at 0° C. The reactionmixture was poured into water and extracted with ethyl acetate. Theorganic layer was washed with a saturated aqueous solution of sodiumchloride, dried over anhydrous magnesium sulfate and concentrated. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=10:1) to give the title compound (0.89 g) havingthe following physical data.

TLC: Rf 0.69 (hexane:ethyl acetate=5:1);

NMR (300 MHz, CDCl₃): δ 7.34 (d, J=8.7 Hz, 1H), 6.91 (d, J=2.7 Hz, 1H),6.73 (d, J=8.7 Hz, 2.7 Hz, 1H), 3.79 (s, 3H), 2.10 (s, 3H).

REFERENCE EXAMPLE 115-bis(trimethylsilyl)amino-2-cyano-3-methyl-4-(2-chloro-4-methoxyphenyl)pyrrole

Under argon atmosphere, diisobutyl aluminum hydride (13.8 ml) was addedslowly to nickel chloride (832 g), which was dried with heating for 30minutes, and then the mixture was stirred for 15 minutes. After a colorof the mixture was changed to black, the compound prepared in Referenceexample 10 (11.6 g) in trimethylsilyl cyanide (46 ml) was added over 25minutes to the reaction mixture. The mixture was heated, and hexane wasdistilled off. The solution was stirred for 2.5 hours at 130° C. Thereaction mixture was cooled at room temperature, and diluted withmethylene chloride. The diluted solution was purified by columnchromatography on silica gel (hexane:ethyl acetate=10:1) to give thetitle compound (9.5 g) having the following physical data and2-bis(trimethylsilyl)amino-5-cyano-3-methyl-4-(2-chloro-4-methoxyphenyl)pyrrole(5.2 g) as by-product.

TLC: Rf 0.34 (hexane:ethyl acetate=10:1);

NMR (300 MHz, CDCl₃): δ 7.76 (brs, 1H), 7.10 (d, J=8.4 Hz, 1H), 7.00 (d,J=2.7 Hz, 1H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 3.83 (s, 3H), 2.06 (s, 3H),0.14 (s, 9H), −0.14 (s, 9H).

REFERENCE EXAMPLE 125-amino-2-cyano-3-methyl-4-(2-chloro-4-methoxyphenyl)pyrrole

To a solution of the compound prepared in Reference Example 11 (6.27 g)in methanol (50 ml), 1N aqueous solution of sodium hydroxide (15.4 ml)was added at room temperature. The mixture was refluxed with heating for1.5 hours. After the reaction mixture was cooled to room temperature,the reaction mixture was poured into an aqueous solution of sodiumcarbonate, and extracted with ethyl acetate. The organic layer waswashed with a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated to give the title compound(4.78 g) having the following physical data.

TLC: Rf 0.20 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 8.61 (brs, 1H), 7.14 (d, J=8.7 Hz, 1H), 7.03 (d,J=2.4 Hz, 1H), 6.86 (dd, J=8.7, 2.4 Hz, 1H), 3.83 (s, 3H), 3.71 (brs,2H), 2.04 (s, 3H).

EXAMPLE 161-cyano-2-methyl-8-hydroxy-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,2-a]pyrimidine

The title compound (1.35 g) was obtained by the same procedure as areaction of Example 1, using the compound prepared in Reference Example12 (4.15 g).

TLC: Rf 0.15 (hexane:ethyl acetate=1:1);

NMR (300 MHz, DMSO-d₆): δ 12.25 (brs, 1H), 7.31 (d, J=7.8 Hz, 1H), 7.20(d, J=2.7 Hz, 1H), 7.02 (dd, J=7.8, 2.7 Hz, 1H), 3.83 (s, 3H), 2.83 (m,2H), 2.66 (m, 2H), 2.06 (s, 3H), 2.03 (m, 2H).

EXAMPLE 171-cyano-2-methyl-8-(3-pentylamino)-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,2-a]pyrimidine

The title compound (112 mg) was obtained by the same procedure as areaction of Example 2, using1-cyano-2-methyl-8-chloro-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrrolo[1,2-a]pyrimidine(180 mg) which was prepared by the same procedure as a reaction ofReference Example 7 using the compound prepared in Reference example 16.

TLC: Rf 0.36 (toluene:ethyl acetate=9:1);

NMR (300 MHz, CDCl₃): δ 7.25 (d, J=8.4 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H),6.88 (dd, J=8.4, 2.4 Hz, 1H), 5.94 (d, J=9.0 Hz, 1H), 3.83 (s, 3H), 3.82(m, 1H), 3.04 (m, 2H), 2.87 (m, 2H), 2.29 (s, 3H), 2.11 (m, 2H),1.82–1.60 (m, 4H), 1.04 (t, J=7.5 Hz, 3H), 1.03 (t, J=7.5 Hz, 3H).

EXAMPLE 17(1)1-cyano-2-methyl-8-dipropylamino-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,2-a]pyrimidine

The title compound having the following physical data was obtained bythe same procedure as a series of reactions of Reference Example8→Reference Example 9→Reference Example 10→Reference Example11→Reference Example 12→Example 16→Example 17, using a correspondingcompound.

TLC: Rf 0.39 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.26 (d, J=8.1 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H),6.89 (dd, J=8.1, 2.4 Hz, 1H), 3.84 (s, 3H), 3.35–3.13 (m, 4H), 3.00–2.80(m, 4H), 2.32 (s, 3H), 2.14 (m, 2H), 1.81–1.38 (m, 4H), 0.91 (t, J=7.5Hz, 6H).

REFERENCE EXAMPLE 135-amino-4-cyano-2,3-dimethyl-1-(2-methyl-4-methoxyphenyl)pyrrole

To a solution of 2-methyl-4-methoxyaniline (10 g) in toluene (120 ml),acetoin and p-toluenesulfonic acid hydrate (44 mg) were added. Themixture was refluxed with heating for 2 hours. After the reactionmixture was cooled to room temperature, malononitrile (4.6 ml) was addedto the reaction mixture, and it was refluxed with heating for 12 hours.The cooled reaction mixture was concentrated. The residue was dilutedwith ether, and filtered to give the title compound (5.73 g) having thefollowing physical data

TLC: Rf 0.65 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.07 (d, J=8.4 Hz, 1H), 6.87 (d, J=3.0 Hz, 1H),6.82 (dd, J=3.0, 8.4 Hz, 1H), 3.84 (s, 3H), 3.71 (brs, 2H), 2.06 (s,3H), 1.99 (s, 3H), 1.73 (s, 3H).

EXAMPLE 182,3-dimethyl-4-amino-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

To a solution of the compound prepared in Reference Example 13 (4.0 g)in benzene (40 ml), cyclopentanone (1.46 ml) and p-toluenesulfonic acidhydrate (40 mg) were added. The mixture was refluxed with heating anddehydrating for 12 hours. An insoluble matter was removed by filtrationthrough celite, and the filtrate was concentrated. Under an argonatmosphere, 2M lithium diisopropylamide (15.7 ml; in THF) was added to asolution of the residue in anhydrous tetrahydrofuran (80 ml) at 0° C.,and then the mixture was warmed to room temperature and stirred for 5days. Water was added to the reaction mixture, and the mixture wasextracted with ethyl acetate. The extract was washed with water and asaturated aqueous solution of sodium chloride, successively, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (ethyl acetate) to give the titlecompound (2.85 g) having the following physical data

TLC: Rf 0.51 (chloroform:methanol=10:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.85 (d, J=3.0 Hz, 1H),6.80 (dd, J=3.0, 8.4 Hz, 1H), 4.31 (s, 2H), 3.83 (s, 3H), 2.90 (m, 2H),2.74 (m, 2H), 2.48 (s, 3H), 2.10 (m, 2H), 1.97 (s, 3H), 1.90 (s, 3H).

EXAMPLE 192,3-dimethyl-4-ethylcarbonylamino-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

To a solution of the compound prepared in Example 18 (600 mg) in THF (60ml), triethylamine (520 μl) and propionyl chloride (180 μl) were added.The mixture was stirred for 2 hours. The reaction mixture was dilutedwith ethyl acetate, and the diluted solution was washed with a saturatedaqueous solution of sodium bicarbonate and with a saturated aqueoussolution of sodium chloride, successively, dried over anhydrousmagnesium sulfate and concentrated. The residue was washed with hexaneto give the title compound (451 mg) having the following physical data.

TLC: Rf 0.60 (chloroform:methanol=10:1);

NMR (300 MHz, CDCl₃): δ 7.30 (m, 1H), 7.08 (d, J=8.4 Hz, 1H), 6.87 (d,J=2.7 Hz, 1H), 6.83 (dd, J=2.7, 8.4 Hz, 1H), 3.84 (s, 3H), 2.98 (t,J=7.2 Hz, 2H), 2.87 (m, 2H), 2.51 (m, 2H), 2.37 (s, 3H), 2.09 (m, 2H),2.02 (s, 3H), 1.88 (s, 3H), 1.33 (m, 3H).

EXAMPLE 202,3-dimethyl-4-propylamino-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

To a solution of the compound prepared in Example 19 (451 mg) in THF(5.0 ml), 2M borane dimethylsulfide complex (4.8 ml; in THF) was added,and the mixture was refluxed with heating for 5 hours. Methanol wasadded to the reaction mixture, and then the mixture was refluxed withheating for 2 hours. After the reaction mixture was cooled, the mixturewas diluted with ethyl acetate. The diluted solution was washed withwater and a saturated aqueous solution of sodium chloride, dried overanhydrous magnesium sulfate and concentrated. The residue was purifiedby column chromatography on silica gel (hexane:ethyl acetate=1:1) togive the title compound (268 mg) having the following physical data.

TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.09 (d, J=8.7 Hz, 1H), 6.85 (d, J=2.7 Hz, 1H),6.80 (dd, J=2.7, 8.7 Hz, 1H), 3.83 (s, 3H), 3.43 (m, 2H), 3.05 (m, 2H),2.84 (m, 2H), 2.48 (s, 3H), 2.04 (m, 2H), 1.97 (s, 3H), 1.90 (s, 3H),1.65 (m, 2H), 1.02 (t, J=7.5 Hz, 3H).

EXAMPLE 212,3-dimethyl-4-(N-ethylcarbonyl-N-propylamino)-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

Under argon atmosphere, triethylamine (360 μl) and propionyl chloride(134 μl) were added to a solution of the compound prepared in Example 20(234 mg) in methylene chloride (3.0 ml) at 0° C. The mixture was stirredfor 1 hour. The reaction mixture was diluted with ethyl acetate, and thediluted solution was washed with a saturated aqueous solution of sodiumbicarbonate, water and a saturated aqueous solution of sodium chloride,successively, dried over anhydrous magnesium sulfate and concentrated.The residue was purified by column chromatography on silica gel(hexane:ethyl acetate=2:1) to give the title compound (242 g) having thefollowing physical data.

TLC: Rf 0.57 (hexane:ethyl acetate=1:1);

NMR (300 MHz, CDCl₃): δ 7.11 (m, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.85 (dd,J=2.4, 8.4 Hz, 1H), 3.92 (m, 1H), 3.86 (s, 3H), 3.42 (m, 1H), 3.01 (t,J=7.8 Hz, 2H), 2.87 (m, 2H), 2.20 (s, 3H), 1.94–2.20 (m, 4H), 2.05 (s,3H), 1.92 and 1.90 (s, total 3H), 1.63 (m, 2H), 0.99–1.10 (m, 3H),0.85–0.94 (m, 3H).

EXAMPLE 222,3-dimethyl-4-dipropylamino-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

The title compound (182 mg) having the following physical data wasobtained by the same procedure as a reaction of Example 20, using thecompound prepared in Example 21 (242 mg).

TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.87 (d, J=2.7 Hz, 1H),6.81 (dd, J=8.4, 2.7 Hz, 1H), 3.84 (s, 3H), 3.17 (m, 4H), 2.95 (t, J=7.5Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.44 (s, 3H), 2.05 (m, 2H), 2.01 (s,3H), 1.92 (s, 3H), 1.52 (m, 4H), 0.85 (t, J=7.2 Hz, 6H).

EXAMPLE 22(1)2,3-dimethyl-4-(N-ethyl-N-pentylamino)-1-(2-methyl-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[e]pyrrolo[2,3-b]pyridine

The title compound having the following physical data was obtained bythe same procedure as a series of reactions of Example 19→Example20→Example 21→Example 22, using a compound prepared in Example 18 and acorresponding compound.

TLC: Rf 0.41 (hexane:ethyl acetate=3:1);

NMR (300 MHz, CDCl₃): δ 7.10 (d, J=8.4 Hz, 1H), 6.86 (d, J=2.7 Hz, 1H),6.81 (dd, J=8.4, 2.7 Hz, 1H), 3.84 (s, 3H), 3.27 (q, J=6.9 Hz, 2H), 3.18(m, 2H), 2.95 (t, J=7.2 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.44 (s, 3H),2.05 (m, 2H), 2.00 (s, 3H), 1.91 (s, 3H), 1.50 (m, 2H), 1.38–1.20 (m,4H), 1.05 (t, J=6.9 Hz, 3H), 0.86 (t, J=6.9 Hz, 3H).

FORMULATION EXAMPLE FORMULATION EXAMPLE 1

The following components were admixed in conventional method and punchedout to obtain 100 tablets each containing 50 mg of active ingredient.

8-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)- 5.0 g 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidineCarboxymethylcellulose calcium (disintegrating agent) 0.2 g Magnesiumstearate (lubricating agent) 0.1 g Microcrystalline cellulose 4.7 g

FORMULATION EXAMPLE 2

The following components were admixed in conventional method. Thesolution was sterilized in conventional manner, placed 5 ml portionsinto ampoules and freeze-dried to obtain 100 ampoules each containing 20mg of the active ingredient.

8-(3-pentylamino)-2-methyl-3-(2-methyl-4-methoxyphenyl)- 2.0 g 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine mannitol 20 gdistilled water 500 ml

1.8-(3-Pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine,a pharmaceutically acceptable salt thereof or a hydrate thereof.
 2. Apharmaceutical composition which comprises8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine,a pharmaceutically acceptable salt thereof or a hydrate thereof, and apharmaceutically acceptable carrier.